Systematic Reviews Open Access
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 10, 2015; 6(5): 759-773
Published online Jun 10, 2015. doi: 10.4239/wjd.v6.i5.759
Diabetic nephropathy in Africa: A systematic review
Jean Jacques N Noubiap, Internal Medicine Unit, Edéa Regional Hospital, PO BOX 100 Edéa, Cameroon
Jashira Naidoo, Department of Medicine, Groote Schuur Hospital, University of Cape Town, 7925 Observatory, Cape Town, South Africa
Jashira Naidoo, Andre P Kengne, Non-Communicable Diseases Research Unit, South African Medical Research Council, 7505 Cape Town, South Africa
Author contributions: All authors contributed to this work.
Conflict-of-interest: None for all co-authors.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Andre P Kengne, Professor, Medical Research Council of South Africa, PO Box 19070 Tygerberg, 7505 Cape Town, South Africa. andre.kengne@mrc.ac.za
Telephone: +27-21-9380529 Fax: +27-21-9380460
Received: December 8, 2014
Peer-review started: December 9, 2014
First decision: January 20, 2015
Revised: February 18, 2015
Accepted: March 16, 2015
Article in press: March 18, 2015
Published online: June 10, 2015
Processing time: 193 Days and 1 Hours

Abstract

AIM: To determine the prevalence and incidence of diabetic nephropathy in Africa.

METHODS: We performed a systematic narrative review of published literature following the MOOSE Guidelines for Meta-Analysis and Systematic Reviews of Observational Studies. We searched PubMed-MEDLINE for all articles published in English and French languages between January 1994 and July 2014 using a predefined strategy based on the combination of relevant terms and the names of each of the 54 African countries and African sub-regions to capture the largest number of studies, and hand-searched the reference lists of retrieved articles. Included studies reported on the prevalence, incidence or determinants of chronic kidney disease (CKD) in people with diabetes within African countries.

RESULTS: Overall, we included 32 studies from 16 countries; two being population-based studies and the remaining being clinic-based surveys. Most of the studies (90.6%) were conducted in urban settings. Methods for assessing and classifying CKD varied widely. Measurement of urine protein was the most common method of assessing kidney damage (62.5% of studies). The overall prevalence of CKD varied from 11% to 83.7%. Incident event rates were 94.9% for proteinuria at 10 years of follow-up, 34.7% for end-stage renal disease at 5 years of follow-up and 18.4% for mortality from nephropathy at 20 years of follow-up. Duration of diabetes, blood pressure, advancing age, obesity and glucose control were the common determinants of kidney disease.

CONCLUSION: The burden of CKD is important among people with diabetes in Africa. High quality data from large population-based studies with validated measures of kidney function are still needed to better capture the magnitude and characteristics of diabetic nephropathy in Africa.

Key Words: Diabetes; Diabetes nephropathy; Chronic kidney disease; Epidemiology; Prevalence; Incidence; Mortality; Africa; Systematic review

Core tip: Chronic kidney disease is a serious health threat for people with diabetes in Africa, with prevalence figures ranging from 11% to 83.7%. The incidence estimates suggest that 95% of people with diabetes may have proteinuria after 10 years from diabetes diagnosis; about 35% may develop end-stage renal disease after 5 years and 18% die from nephropathy after 20 years of disease duration. Hypertension, obesity, poor glycemic control and diabetes duration are the main risk factors of chronic kidney disease among diabetic patients in Africa. High quality data are needed to refine the epidemiology of diabetic nephropathy on the continent.



INTRODUCTION

Africa, like the rest of the world, is experiencing an increasing prevalence of diabetes alongside other non-communicable diseases, mainly as a result of urbanization, sedentary lifestyles, obesity and population growth and ageing[1]. Estimates for 2013 by the International Diabetes Federation (IDF) indicate that the number of adults with diabetes in the world will expand by 55%, from 381.8 million in 2013 to 591.9 million in 2035[2]. The largest increase of the population with diabetes will occur in sub-Saharan Africa, with a projected growth of 109.6%, from 19.8 million in 2013 to 41.5 million in 2035[2].

Diabetes causes significant morbidity, disability and early mortality. Diabetes has been identified as a major contributor in several other important diseases, both non-communicable diseases such as cardiovascular disease and renal disease[3,4], and communicable diseases such as invasive bacterial infections[5,6]. Mortality attributable to diabetes in sub-Saharan Africa was estimated to account for 8.6% of the total death in 2013[7]. Diabetic nephropathy (DN) is one of the most common complications of diabetes. The prevalence of DN is increasing steeply along with the diabetes epidemic[8]. Approximately one third to half of patients with diabetes develops renal manifestations[8-11]. DN is associated with increased premature mortality, end-stage renal disease and need to renal replacement therapy, cardiovascular diseases, and escalating health-care costs[8].

DN has been suggested to be more frequent among patients with diabetes in Africa as compared to those in the developed world due to delayed diagnosis, limited screening and diagnostic resources, poor control of blood sugar and other risk factors, and inadequate treatment at an early stage[7,12,13]. However, evidence to support the burden of kidney diseases in people with diabetes in Africa remains very patchy, and we are not aware of any effort to synthesize existing data on the occurrence of kidney disease in African populations with diabetes. Accordingly, the aim of this review is to provide a comprehensive overview of the published evidence on the occurrence of nephropathy in African people with diabetes.

MATERIALS AND METHODS
Data sources and search strategy

A systematic narrative review of published literature was performed following the MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies[14]. We searched MEDLINE via PubMed for articles published in English and French on DN in Africa between January 1994 and July 2014, using a predefined strategy based on the combination of relevant terms and the names of each of the 54 African countries and African sub-regions to capture the largest number of studies. The data search was limited to human studies. The last search date was October 22, 2014. Search histories are provided in Table 1. Once duplicate references were removed the titles and abstracts of the references were screened. The references of included articles were scanned to identify additional articles of interest.

Table 1 Search history PubMed.
SearchSearch termsHits
1Diabetes[tw] OR Diabetes mellitus[tw] OR Type 1 diabetes[tw] OR Type 1 diabetes mellitus[tw] OR T1DM[tw] OR Type 2 diabetes[tw] OR Type 2 diabetes mellitus[tw] OR T2DM[tw] OR Hyperglycemia[tw] OR Glucose intolerance[tw]445204
2Renal insufficiency[tw] OR Renal failure[tw] OR Renal injury[tw] OR Renal disease[tw] Kidney insufficiency[tw] OR Kidney failure[tw] OR Kidney injury[tw] OR Kidney disease[tw] OR End-stage renal disease[tw] OR End-stage renal failure[tw] OR End-stage kidney disease[tw] OR End-stage kidney failure [tw] OR End stage renal disease[tw] OR End stage renal failure[tw] OR End stage kidney disease[tw] OR End stage kidney failure [tw] OR Microalbuminuria [tw] OR Micro-albuminuria OR Macroalbuminuria [tw] or Macro-albuminuria [tw]154354
3# 1 AND # 220388
4Diabetic nephropathy [MeSH Terms]19406
5# 3 OR # 434221
6((((("Africa"[MeSH] OR Africa*[tw] OR Algeria[tw] OR Angola[tw] OR Benin[tw] OR Botswana[tw] OR "Burkina Faso"[tw] OR Burundi[tw] OR Cameroon[tw] OR "Canary Islands"[tw] OR "Cape Verde"[tw] OR "Central African Republic"[tw] OR Chad[tw] OR Comoros[tw] OR Congo[tw] OR "Democratic Republic of Congo"[tw] OR Djibouti[tw] OR Egypt[tw] OR "Equatorial Guinea"[tw] OR Eritrea[tw] OR Ethiopia[tw] OR Gabon[tw] OR Gambia[tw] OR Ghana[tw] OR Guinea[tw] OR "Guinea Bissau"[tw] OR "Ivory Coast"[tw] OR "Cote d'Ivoire"[tw] OR Jamahiriya[tw] OR Jamahiryia[tw] OR Kenya[tw] OR Lesotho[tw] OR Liberia[tw] OR Libya[tw] OR Libia[tw] OR Madagascar[tw] OR Malawi[tw] OR Mali[tw] OR Mauritania[tw] OR Mauritius[tw] OR Mayote[tw] OR Morocco[tw] OR Mozambique[tw] OR Mocambique[tw] OR Namibia[tw] OR Niger[tw] OR Nigeria[tw] OR Principe[tw] OR Reunion[tw] OR Rwanda[tw] OR "Sao Tome"[tw] OR Senegal[tw] OR Seychelles[tw] OR "Sierra Leone"[tw] OR Somalia[tw] OR "South Africa"[tw] OR "St Helena"[tw] OR Sudan[tw] OR Swaziland[tw] OR Tanzania[tw] OR Togo[tw] OR Tunisia[tw] OR Uganda[tw] OR "Western Sahara"[tw] OR Zaire[tw] OR Zambia[tw] OR Zimbabwe[tw] OR "Central Africa"[tw] OR "Central African"[tw] OR "West Africa"[tw] OR "West African"[tw] OR "Western Africa"[tw] OR "Western African"[tw] OR "East Africa"[tw] OR "East African"[tw] OR "Eastern Africa"[tw] OR "Eastern African"[tw] OR "North Africa"[tw] OR "North African"[tw] OR "Northern Africa"[tw] OR "Northern African"[tw] OR "South African"[tw] OR "Southern Africa"[tw] OR "Southern African"[tw] OR "sub Saharan Africa"[tw] OR "sub Saharan African"[tw] OR "subSaharan Africa"[tw] OR "subSaharan African"[tw]) NOT ("guinea pig"[tw] OR "guinea pigs"[tw] OR "aspergillus niger"[tw])))))354928
7# 5 AND # 61065
8#4 Limits: 1994/01/01 to 2014/10/22 and studies done in Humans918
Study selection and data extraction

We included cross-sectional, case-control or cohort studies of subjects with diabetes mellitus resident in African countries reporting the prevalence or incidence or progression of DN. We excluded studies of populations of African origin residing outside Africa; case series (sample size less than 50 subjects), letters, comments and editorials; studies not published in English or French. Two investigators (JJNN, APK) independently identified articles and sequentially screened them for inclusion (Figure 1). Disagreements were solved by a third investigator (JN). Full text articles were reviewed by two investigators (JJNN and APK) who independently extracted data regarding study setting and design, study population characteristics and prevalence or incidence of DN.

Figure 1
Figure 1 Flow diagram of study selection.
RESULTS

We identified 730 articles, of which 73 were reviewed in full-text; 32 met the inclusion criteria (Figure 1)[15-46].

Characteristics of included studies

Characteristics of the included studies are summarized in Table 2. The 32 studies were performed in 16 countries, with a geographical distribution covering all the African regions. However, more than half the studies [18 (56.3%)] were from South Africa (five), Nigeria (four), DR Congo (three) and Ethiopia (three).

Table 2 General characteristics of studies of chronic kidney disease in people with diabetes in Africa.
Ref.CountryPeriodDesignSettingSample sizeMean or median age (yr)Male (%)Type and duration of diabetes (yr)Duration FUPMethod for CKD assessment
ProteinuriaMDRDUrine ACRCockroft-Gault
Motala et al[37], 2001South AfricaNot precisedRetrospective cohort studyClinic, urban21939.5 T1DM; 58.4 T2DM19.616.10 T1DM; 18.6 T2DMAt least 10 yrpersistent proteinuria (Dipstick)
Elbagir et al[26], 1995SudanJan-July 1992Cross-sectional, self-selected samplingClinic, urban12831.5 (15-75)48.4Insulin-treated; 9 (1-40)NAProteinuria (Dipstick)
Sobngwi et al[44], 1999CameroonNot precisedCross-sectional, self-selected samplingClinic, urban6437.4 normotensive T1DM; 51.7 normotensive T2DM; 57.9 hypertensive T1DM57.86.7 normotensive T1DM; 4.7 normotensive T2DM; 4.8 hypertensive T1DMNAProteinuria
Katchunga et al[30], 2010DR congo2005-2007Cross-sectional, self-selected samplingClinic, urban9858 (10.4)35.77.3 T2DMNAMDRD (corrected for Blacks)
Choukem et al[22], 2012CameroonJan 2008- Oct 2010Cross-sectional, self-selected samplingClinic, urban42056.7494 (1-9) T2DMNAProteinuria (Dipstick)
Keeton et al[31], 2004South AfricaNot precisedProspective cohort, self-selected samplingClinic, urban596235.617.8 T2DM12 yrUrine ACR
Pruijm et al[39], 2008Seychelles2004Cross-sectional; random sex and age-stratified samplePopulation1218 (whole sample, including diabetic patients)Not precised45.9Newly diagnosed patientsNAUrine ACR
Alebiosu[16], 2003NigeriaJan 2000 June 2001Cross-sectional, self-selected samplingClinic, urban3426.5 T1DM; 9.4 T2DM53.826 T1DM; 53.4 T2DMNAPersistent proteinuria
Bouaziz et al[20], 2012TunisiaJan 2008Dec 2010Cross-sectional, self-selected samplingClinic, urban7359.323.3T2DM 10.6NAProteinuria
Ajayi et al[15], 2014NigeriaNot precisedRetrospective cross-sectionalClinic, urban65Not availableNot availableT2DMNAMDRD
Levitt et al[32], 1997South AfricaJuly-December 1992Cross-sectional, stratified random samplingClinic, urban24356.438.38 T2DM and T1DMNAPersistent proteinuriaUrine ACR
Majaliwa et al[34], 2007TanzaniaJune 2005- Feb 2006Cross-sectional, self-selected samplingClinic, urban9912.642.44.76 T1DMNAProteinuria
Marshall et al[36], 2013RwandaJune 2009-Nov 2010Cross-sectional, self-selected samplingClinic, urban28618.646.53.4 T1DMNAProteinuriaUrine ACR
Alebiosu et al[18], 2003NigeriaSept 1999- August 2002Cross-sectional, self-selected samplingClinic, urban465Not precisedNot precisedT2DMNAProteinuria
Gill et al[28], 2005South AfricaFrom 1982 to 2002Prospective cohort, self-selected samplingClinic, urban8822 at onset52T1DM20 yr
Djrolo et al[24], 2001BeninNot indicatedCross-sectionalClinic, urban15253.365.8T1DM and T2DMNAProteinuria
Rotchford et al[43], 2002South Africa1999Cross-sectional, self-selected samplingClinic, rural25356.526.942.2; T1DM and T2DMNAUrine ACR
Rissassi et al[42], 2009DR congo11 june 2008 to 30 july 2008Cross-sectional, self-selected samplingClinic, urban18119.138.757.6 T1DMNAUrine ACR
Rahlenbeck et al[40], 1997EthiopiaJanuary - April 1995Cross-sectional, self-selected samplingClinic, urban17031.4 T1DM; 56.7 T2DM605.9 T1DM; 6.0 T2DMNAProteinuria
Wanjohi et al[45], 2002KenyaJune 2000 - January 2001cross-sectional, self-selected samplingClinic, urban10053.73710.3 T2DMNAAlbuminuria
Nambuya et al[38], 1996Uganda1 January 1993 - 10 August 1994Cross-sectional, self-selected samplingClinic, urban/urban (origin of participants)252Not precised46.445 (range 30-69)T2DM and T1DMNAProteinuria
Rasmussen et al[41], 2013ZambiaFebruary - April 2011Cross-sectional, self-selected samplingClinic, rural10150 (range 50-68)37.3T2DM and T1DMNAUrine ACR
Bentata et al[19], 2013MoroccoFrom September 2006Prospective cohort studyClinic, urban7229.569.417 (11-20) T1DM5 yrProteinuriaMDRD
Gill et al[27], 2008EthiopiaNot precisedCross-sectional, self-selected samplingClinic, rural1054170.57 T1DM and T2DMNAUrine ACR
Bouzid et al[21], 2011TunisiaJune 2006 - July 2008Cross-sectional, self-selected samplingClinic, urban6896039.311 T2DMNAProteinuriaCockroft-Gault
Janmohamed et al[29], 2013TanzaniaOctober 2011 - March 2012Cross-sectional, self-selected samplingClinic, urban36954 (IQR 45-62)46.66 (3-11)T1DM (6.2%) and T2DM (93.8%)NACockroft-Gault
Danquah et al[23], 2012GhanaAugust 2007 - June 2008Cross-sectional, self-selected samplingClinic, urban67554.725T2DMNAProteinuria
Lutale et al[33], 2007TanzaniaJuly 2003 - March 2004Cross-sectional, self-selected samplingClinic, urban244T1DM 21(range 4-44.8)T2DM 53 (range 23.5-85)46.3T1DM 3 (0-17)T2DM 4 (range 0-25)NAProteinuriaCockroft-Gault
Worku et al[46], 2010EthiopiaOctober 2008Cross-sectional, self-selected samplingClinic, urban30544.462.9T1DM and T2DM; 53.4% less than 5 yr and 33.8% 5-9 yrNAProteinuria
Makulo et al[35], 2010DR Congo30 March - 24 April 2007Cross-sectional, self-selected samplingPopulation-based, Urban81Not precisedNot precisedNo precisionNAMDRDUrine ACR
Eghan et al[25], 2007GhanaJanuary - July 2005Cross-sectional, self-selected samplingClinic, urban10954.128T1DM and T2DM 10.7NAProteinuria
Alebiosu et al[17], 2004NigeriaJanuary 2000 - June 2001Case (T2DM with persistent proteinuria-control (T2DM patients nephropathy)Clinic, urban16253.450T2DM9.4 cases, 5.5 controlsNA

Only two population-based studies were identified. In Democratic Republic of Congo, between March and April 2007, Makulo et al[35] studied pathologic albuminuria among 81 diabetic patients identified through a population-based survey on the prevalence of diabetes involving 1898 participants[35]. Pruijm et al[39] in Seychelles in 2004, conducted a large-scale population-based estimate of the prevalence of microalbuminuria among 1218 adults. All other studies were clinic-based surveys conducted mostly in diabetic clinics. There were three cohort studies (two prospective and one retrospective), one case-control study and the other 28 studies were cross-sectional with non-random sampling. Only three (9.4%) studies were conducted in rural settings.

Methods of assessment and classification of chronic kidney disease (CKD) varied widely. The studies assessed kidney function by urine protein [20 (62.5%) studies], urine albumin-to-creatinine ration (ACR) [9 (28.1%) studies], and estimation of glomerular filtration rate (GFR) by Cockcroft-Gault formula [3 (9.4%) studies] or by MDRD formula [4 (12.4%) studies]. Six studies (18.8%) measured kidney function by two methods, and renal biopsy was not performed in any study.

Prevalence of CKD

As depicted in Table 3, the overall prevalence of CKD varied from 11% in Tunisia to 83.7% in Tanzania[20,29]. In studies where proteinuria was used to assess CKD, the prevalence varied from 5.3% in South Africa to 53.1% in Cameroon (study with a small sample size)[32,44]. When considering the estimation of the GFR, the prevalence ranged from 4.6% in Tanzania to 43.1% in Nigeria (study with a small sample size)[15,33].

Table 3 Prevalence and incidence of chronic kidney disease in people with diabetes across studies in Africa.
Ref.CountrySample sizeType of diabetesDuration of follow-upDiagnostic criteria for CKDPrevalenceIncidenceComments
Motala et al[37], 2001South Africa219T1DM and T2DM16.10 (4.9) T1DM; 18.6 (5.7) T2DM; at least 10 yrPersistent proteinuria (dipstix proteinuria on three or more consecutive occasions over 18 mo in the at absence of infection or cardiac failure)Not applicable24.6%
Elbagir et al[26], 1995Sudan128Insulin-treatedNot applicableProteinuria (≥ 30 mg/dL)22%Not applicable
Sobngwi et al[44], 1999Cameroon64T1DM and T2DMNot applicableProteinuria53.1%Not applicable
Katchunga et al[30], 2010DR Congo98T2DMNot applicableMDRD: CKD stage ≥ 2 according to the National Kidneyfoundation18.1%Not applicable
Choukem et al[22], 2012Cameroon420T2DMNot applicableProteinuria (30 mg/24 h)31%Not applicable
Keeton et al[31], 2004South Africa59T2DM12 yrUrine Albumin-to-Creatinine Ratio (no detail)After 12 yr of follow-up or death, 94.9% (56/59) had a proteinuria with a mean duration from diabetes onset to proteinuria of 9.7 (5.9) yr83% (49/59) had an elevated SCr atthe end of the study and in 66.1% (39/59) the SCr level had doubled during the study
Pruijm et al[39], 2008Seychelles1218All typesNot applicableMicroalbuminuria: Urine Albumin-to-Creatinine Ratio 3.4-33.9 mg albumin/mmol creatinine36.1%Not applicable
Alebiosu[16], 2003Nigeria342T1DM and T2DMNot applicablePersistent proteinuria28.4%Not applicable
Bouaziz et al[20], 2012Tunisia73T2DMNot applicableMicroalbuminuria: < 2.8 g/mol for women and < 2.3 g/mol for men11%Not applicable
Ajayi et al[15], 2014Nigeria65T2DMNot applicableMDRD: eGFR ≤ 60 mL/min per 1.73 m243.1%Not applicable
Levitt et al[32], 1997South Africa243T2DM and T1DMNot applicableUrine Albumin-to-Creatinine Ratio > 3.4 mm/mmol36.7%Not applicable
Persistent proteinuria (for at least 3 consecutive visits)5.3%
Majaliwa et al[34], 2007Tanzania99T1DMNot applicableProteinuria (no detail)29.3%Not applicable
Marshall et al[36], 2013Rwanda286T1DMNot applicableMicroalbuminuria: Urine Albumin-to-Creatinine Ratio = 30-299 mg/gMacroalbuminuria or overt nephropathy: Urine Albumin-to-Creatinine Ratio ≥ 300 mg/gMicroalbuminuria: 21%; Macroalbuminuria: 5%Not applicable
Alebiosu et al[18], 2003Nigeria465T2DMNot applicableProteinuria and eGFR41.1%Not applicableThe method for the estimation of the GFR is not indicated
Gill et al[28], 2005South Africa88T1DM20 yrPersistent dipstick proteinuriaDeath of renal cause after 20 yr = 18.4% (9/49)Death due to chronic renal failure after 20 yr of follow-up was 9/49 (after exclusion of lost to follow)
Djrolo et al[24], 2001Benin152T1DM and T2DMNot applicableProteinuria (no detail)20%Not applicable
Rotchford et al[43], 2002South Africa253T1DM and T2DMNot applicableMicroalbuminuria > 2.5 mg/mmol in men or 3.5 mg/mmol in women46.4%Not applicable
Rissassi et al[42], 2009DR congo181T1DMNot applicableMicroalbuminuria: Urine Albumin-to-Creatinine Ratio = 30-299 mg/gMacroalbuminuria: Urine Albumin-to-Creatinine Ratio ≥ 300 mg/g21.9% (microalbuminuria) and 7.3% (macroalbuminuria)Not applicable
Rahlenbeck et al[40], 1997Ethiopia170T1DM and T2DMNot applicableMicroalbuminuria: > 30 mg/LMacroalbuminuria: > 300 mg/LT1DM: 32% (microalbuminuria) and 15% (macroalbuminuria)T2DM: 37% (microalbuminuria) and 20% (macroalbuminuria)Not applicable
Wanjohi et al[45], 2002Kenya100T2DMNot applicableProteinuria ≥ 20 mg26%Not applicable
Nambuya et al[38], 1996Uganda252T1DM and T2DMNot applicableProteinuria (no detail)17.1%Not applicableNewly diagnosed patients
Rasmussen et al[41], 2013Zambia101T1DM and T2DMNot applicableMicroalbuminuria: ACR = 3.5-35.0 for women and 2.5-25.0 mg/mmol for menMacroalbuminuria were ACR> 35.0 for women and > 25.0 for menMicroalbuminuria: 23.8%Macroalbuminuria: 8.9%Not applicableThere were 33 patients with diabetes alone, and 68 patients with diabetes and hypertension
Bentata et al[19], 2013Morocco72T1DM5 yrMicroalbuminuria: albumin excretion rate 30-300 mg/24 hMacroalbuminuria: albumin excretion rate > 300 mg/24 hNephrotic proteinuria: albumin excretion rate ≥ 3000 mg/24 hRenal failure: eGFR < 60 mL/min (MDRD)At the time of enrollementMicroalbuminuria: 48.6%Macroalbuminuria: 36.1%Nephrotic proteinuria: 15.3%The incidence of end stage renal disease after 5 yr: 34.7%Urinary assays done onadmission were repeated on three specimens atthree-monthly intervals
Gill et al[27], 2008Ethiopia105T1DM and T2DMNot applicableNephropathy: ACR> 25.0 mg/mmol and retinopathy presentMicroalbuminuria: ACR> 2.5 and < 25.0 mg/mmol in men and > 3.5 and< 25.0 mg/mmol in womenNephropathy: 2%Microalbuminuria: 51%Urinary ACR levels (toassess microalbuminuria and nephropathy) were done on59 patients, as those with haematuria and/or urinary infection were excluded
Bouzid et al[21], 2011Tunisia689T2DMNot applicableCKD: eGFR < 60 mL/min per 1.73 m2 (Cockroft-Gault)Microalbuminuria: albumin excretion rate 30-300 mg/24 hMacroalbuminuria: albumin excretion rate > 300 mg/24 hCKD: 19.8%Microalbuminuria: 13%Macroalbuminuria: 10.1%Not applicableMacroalbuminuria was significantly associated with CKD (P < 0.00001)
Janmohamed et al[29], 2013Tanzania369T1DM and T2DMNot applicableCKD: eGFR < 60 mL/min per 1.73 m2 (Cockroft-Gault) or microalbuminuria (> 20 mg/L) or overt protienuriaCKD: 83.7%eGFR < 60 mL/min per 1.73 m2: 24.7%Microalbuminuria: 45.8%Overt proteinuria: 34.1%Not applicable
Danquah et al[23], 2012Ghana671T2DMNot applicableProteinuria ≥ 20 mg/L43%Not applicable
Lutale et al[33], 2007Tanzania244T1DM and T2DMNot applicableMicroalbuminuria: AER 20-200 μg/minMacroalbuminuria: AER > 200 μg/minRenal failure: eGFR < 60 mL/min per 1.73 m2:Microalbuminuria: 12.1% (T1DM); 9.8% (T2DM)Macroalbuminuria: 1.1% (T1DM); 7.2% (T2DM)Renal failure: 4.6% (T1DM); 22% (T2DM)Not applicable
Worku et al[46], 2010Ethiopia305T1DM (38%) and T2DM (62%)Not applicableProteinuria (no detail)15.7%Not applicable
Makulo et al[35], 2010DR Congo81No precisionNot applicableMicroalbuminuria: ACR 30-299 mg/gMacroalbuminuria: ACR ≥ 300 mg/gRenal failure: eGFR < 60 mL/min per 1.73 m2Microalbuminuria: 43.5%Macroalbuminuria: 12%Renal failure: 21.4%Not applicable
Eghan et al[25], 2007Ghana109T1DM and T2DMNot applicableMicroalbuminuria: ACR 30-300 mg/g43.1%Not applicable
Alebiosu et al[17], 2004Nigeria162T2DMNot applicableNot applicableNot applicableNot applicableThe study did not assess the prevalence or incidence of diabetic nephropathy, but its predictors
Incidence of CKD

A study in South Africa investigated the long-term incidence of proteinuria among T2DM patients. After 12 years of follow-up or death, 94.9% (56/59) had a proteinuria with a mean duration from diabetes onset to proteinuria of 9.7 (5.9) years[31]. In another study in South Africa, found that 18.4% of T1DM patients had died from renal nephropathy after 20 years of follow-up[28]. In a recent study in Morocco, the incidence of end-stage renal disease after 5 years was 34.7%[19].

Risk factors of CKD

Twenty studies (62.5%) reported factors associated with CKD in diabetic patients (Table 4). However, in most studies the method to assess this association was imprecise. In cross-sectional studies, correlates of CKD included systolic and diastolic high blood pressure, long duration of diabetes, older age, dyslipidemia, obesity[16-22,25,26,29-31,33,36,40,42-44,46]. In a study in Cameroon, T2DM patients with systolic hypertension and diastolic hypertension were respectively 1.45 (95%CI: 1.15-1.84; P = 0.006) and 1.33 (95%CI: 1.06-1.66; P = 0.026) times more likely to have nephropathy[22]. Two studies in Rwanda and South Africa respectively showed that a one year increase in the duration of T1DM increased by 0.86 (95%CI: 0.77-0.96; P = 0.008) the odds of microalbuminuria[36], and that T1DM and T2DM patients with a duration of diabetes greater than 10 years were 4.19 times (95%CI: 1.93-9.10; P < 0.001) more likely to have microalbuminuria[43]. Poor glycemic control as measured by HbA1c was also a strong predictor of nephropathy. For instance, HbA1c level greater than 10% and 14% were respectively associated with a 2.6 fold (95%CI: 1.1-6.4) and a 4.69 (95%CI: 1.65-13.3; P = 0.004)[42,43]. A 1 g/dL decrease in hemoglobin level has been found to be associated with end-stage renal disease (OR 3.18, 95%CI: 1.47-6.87; P = 0.003)[19]. Studies in Nigeria showed that left ventricular hypertrophy, stroke, myocardial infarction and peripheral arterial disease were more frequent in T2DM patients with nephropathy, especially those with advanced stages[17,18].

Table 4 Risk factors for chronic kidney disease in people with diabetes.
Ref.CountrySample sizeType of diabetesDiagnostic criteria for CKDRisk factorMeasure of association
Factors adjusted forComments
Effect sizeP-value
Motala et al[37], 2001South Africa219T1DM and T2DMPersistent proteinuriaNot assessed
Elbagir et al[26], 1995Sudan128Insulin-treatedProteinuriaAgeP = 0.006
Duration of diabetesP = 0.003
Systolic BPP = 0.0001
Diastolic BPP = 0.001
Serum cholesterolP < 0.05
Sobngwi et al[44], 1999Cameroon64T1DM and T2DMProteinuriaDuration of diabetesP = 0.04
Diastolic BPP = 0.01
Katchunga et al[30], 2010DR Congo98T2DMMDRD (corrected for Blacks); CKD stage ≥ 1 according to the National KidneyfoundationHypertensionaOR: 2.49 (0.98-6.34)P = 0.04Age, duration of diabetes, BMI
Choukem et al[22], 2012Cameroon420T2DMProteinuria (30 mg/24 h)Systolic BPaOR: 1.45 (1.15-1.84)P = 0.006
Diastolic BPaOR: 1.33 (1.06-1.66)P = 0.026
Pulse pressureaOR: 1.35 (1.06-1.71)P = 0.0007
Mean arterial pressureaOR: 1.42 (1.13-1.78)P = 0.006
Keeton et al[31], 2004South Africa59T2DMUrine Albumin-to-Creatinine Ratio (no detail)High entry serum creatinineP < 0.006These are risk factors for death from chronic renal failure (compared with the patients who were still alive at follow-up)By the end of study 47 of the 59 patients had died; the cause of death not established in 2 patients. Death was due to chronic renal failure in 17 cases
BMI < 28P < 0.003
Severe retinopathyP < 0.002
Mean glucose level of > 14 mmol/LP < 0.035
Pruijm et al[39], 2008Seychelles1218All typesMicroalbuminuria: Urine Albumin-to-Creatinine Ratio 3.4-33.9 mg albumin/mmol creatinineNot assessedRisk factors were investigated in the whole study population in both diabetics and non-diabetics
Alebiosu[16], 2003Nigeria342T1DM and T2DMPersistent proteinuriaNot assessed
Bouaziz et al[20], 2012Tunisia73T2DMMicroalbuminuria: < 2.8 g/mol for women and < 2.3 g/mol for menFamily history of nephropathyP = 0.0289Comparison of T2DM patients with nephropathy with those without nephropathy
SmokingP = 0.0056
Insulin therapyP = 0.0310
Glitazones therapyP = 0.0115
Anti-hypertensives (not ACE inhibitor)P < 0.0001
Lipid-lowering agentsP < 0.0001
Ajayi et al[15], 2014Nigeria65T2DMMDRD: eGFR ≤ 60 mL/min per 1.73 m2Not assessed
Levitt et al[32], 1997South Africa243T2DM and T1DMUrine Albumin-to-Creatinine Ratio > 3.4 mm/mmolNot assessed
and Persistent proteinuria (for at least 3 consecutive visits)
Majaliwa et al[34], 2007Tanzania99T1DMProteinuria (no detail)Missing insulin dosesP = 0.045Not available
Marshall et al[36], 2013Rwanda286T1DMMicroalbuminuria: Urine Albumin-to-Creatinine Ratio = 30-299 mg/gAge (increase)aOR: 0.86, 95%CI: 0.77-0.96P = 0.009Each variable is adjusted for the othersThese are risk factors of microalbuminuria. There was no factor associated to macroalbuminuria
Duration of diabetes (one year increase)aOR: 0.86, 95%CI: 0.77-0.96P = 0.008
Diastolic BP (increase)aOR: 0.86, 95%CI: 0.77-0.96P = 0.004
HBA1c (increase)aOR: 0.86, 95%CI: 0.77-0.96P = 0.047
Alebiosu et al[18], 2003Nigeria465T2DMProteinuria and eGFR (no detail)Hypertension, left ventricular hypertrophy, stroke and myocardial infarction were more frequent in advanced stages of nephropathyNot availableP < 0.05Not availablePatients with advanced stages of nephropathy (IV and V) were compared with those with stages ≤ III
Gill et al[28], 2005South Africa88T1DMPersistent dipstick proteinuriaNot assessed
Djrolo et al[24], 2001Benin152T1DM and T2DMProteinuria (no detail)Not availableNot availableNot availableProteinuria was more frequent in insulin-treated patients compared those on oral antidiabetic treatment. The prevalence of proteinuria also increased with the duration of diabetes
Rotchford et al[43], 2002South Africa253T1DM and T2DMMicroalbuminuria > 2.5 mg/mmol in men or 3.5 mg/mmol in womenDuration of diabetes > 10 yr4.19 (1.93-9.10)< 0.001Model contains duration of diabetes, BMI, HbA1c, age andhypertension
BMI > 330.27 (0.08-0.48)0.002
HbA1c > 14%4.69 (1.65-13.3)0.004
Hypertension2.11 (1.07-4.17)0.031
Rissassi et al[42], 2009DR congo181T1DMMicroalbuminuria: Urine Albumin-to-Creatinine Ratio = 30-299 mg/gMacroalbuminuria: Urine Albumin-to-Creatinine Ratio ≥ 300 mg/gDuration of diabetes > 5 yr4.1 (1.9-8.4)No precision
Age > 18 yr2.9 (1.3-6.2)
HbA1c > 10%2.6 (1.1-6.4)
Rahlenbeck et al[40], 1997Ethiopia170T1DM and T2DMalbuminuria: > 30 mg/LDuration of diabetesBeta = 0.061, SE = 0.018 for T1DM< 0.001Hypertensive patients excluded
Systolic blood pressureBeta = 0.027, SE = 0.005 for T1DM< 0.001
Wanjohi et al[45], 2002Kenya100T2DMProteinuria ≥ 20mgNone identified
Nambuya et al[38], 1996Uganda252T1DM and T2DMProteinuria (no detail)None assessed
Rasmussen et al[41], 2013Zambia101T1DM and T2DMMicroalbuminuria: ACR = 3.5-35.0 for women and 2.5-25.0 mg/mmol for menMacroalbuminuria were ACR> 35.0 for women and > 25.0 for menNone assessed
Bentata et al[19], 2013Maroc72T1DMEnd-stage renal disease: eGFR < 15 mL/minHemoglobin blood (per 1 g/dL decrease)3.18 (1.47-6.87)0.003No precisionThese are independent risk factors for ESRD in type-1 diabetes patients with diabetic nephropathy
Diastolic blood pressure (per 1 mmHg increase)1.15 (1.04-1.27)0.006
Gill et al[27], 2008Ethiopia105T1DM and T2DMNephropathy: ACR> 25.0 mg/mmol and retinopathy presentMicroalbuminuria: ACR> 2.5 and < 25.0 mg/mmol in men and > 3.5 and< 25.0 mg/mmol in womenNone assessed
Bouzid et al[21], 2011Tunisia689T2DMRenal failure: creatinine clearance < 60 mL/min (Cockroft-Gault)Older ageNot provided< 0.00001
Hypertension< 0.00001
Long duration of diabetes< 0.001
Higher BMI0.02
Dyslipidemia0.01
Janmohamed et al[29], 2013Tanzania369T1DM and T2DMCKD: eGFR < 60 mL/min per 1.73 m2 (Cockroft-Gault) or microalbuminuria (> 20 mg/L) or overt proteinuriaOlder age1.03 (1.00-1.05)0.03Adjustment made, but no precision
Danquah et al[23], 2012Ghana671T2DMProteinuria ≥ 20mg/lNot assessed
Lutale et al[33], 2007Tanzania244T1DM and T2DMAbnormal proteinuria: AER > 20 μg/minDuration of diabetes0.090 (0.049- 0.131)< 0.0001Predictors in the model: diabetes duration, Systolic BP, age, serum creatinineMeasure of association is β
Elevated systolic blood pressure0.012 (0.003-0.021)0.010
Elevated serum creatinine0.011 (0.002- 0.020)0.016
Worku et al[46], 2010Ethiopia305T1DM and T2DMProteinuria (no detail)Duration of diabetesNot provided0.001
T2DM on insulin0.018
Makulo et al[35], 2010DR Congo81No precisionMicroalbuminuria: ACR 30-299 mg/gMacroalbuminuria: ACR ≥ 300 mg/gRenal failure: eGFR < 60 mL/min per 1.73 m2Not assessed
Eghan et al[25], 2007Ghana109T1DM and T2DMMicroalbuminuria: ACR 30-300 mg/gDuration of diabetes0.04The associations were assessed by comparing patients with and without microalbuminuria
Serum creatinine0.05
Blood urea nitrogen0.01
Urine potassium0.0061
Alebiosu et al[17], 2004Nigeria162T2DMNo precisionDuration of diabetes< 0.05The study assessed the predictors of diabetic nephropathy comparing T2DM patients with and without nephropathy
Serum total cholesterol< 0.05
Alcohol > 30 mg/d< 0.05
Peripheral vascular disease< 0.05
Stroke< 0.05
DISCUSSION

Diabetic nephropathy is a common and morbid complication of diabetes and the leading cause of CKD in the developed world. The lack of renal registries means that there are no reliable statistics about the burden of CKD in people with diabetes in the majority of African countries. The current systematic review identified 32 relevant studies published over the last 20 years on kidney diseases in people with diabetes residing in Africa. Prevalence rates ranged from 11% to 83.7% for the overall CKD, 5.3% to 53.1% for CKD based on proteinuria, and 4.6% to 43.1% for CKD based on eGFR. Incident event rates were 94.9% for proteinuria at 10 years for follow-up, 34.7% for ERSD at 5 years of follow-up and 18.4% for mortality from nephropathy at 20 years of follow-up. Diagnosed duration of diabetes, blood pressure variables, advancing age, obesity and to some extend glucose control were the common determinants of kidney disease in people with diabetes. Studies were overwhelmingly hospital-based studies; half of them originated from four countries while variable definitions and methods for assessing nephropathy had been used across studies.

The most recent overview of CKD in populations within Africa was completed in 2012, and was restricted to sub-Saharan African Countries[47]. This review identified 90 articles representing data from 21 countries, with over half of the studies originating from South Africa, Nigeria and Ethiopia alones. Across 21 studies deemed to be of medium to high quality by the investigators, the pooled prevalence of CKD was 13.9% (95%CI: 12.2-15.7), with substantial heterogeneity across studies. The prevalence in people with diabetes ranged from 4% to 24% based essentially on proteinuria defined CKD[47]. In our review without applying quality criteria, we found much higher prevalence of CKD, regardless of the definition. In four studies published in 2013 for instance, the prevalence of microalbuminuria ranged between 21% and 45%. Although issues with the quality of the studies preclude direct comparisons, it is likely that nephropathy is more frequent in population with diabetes within Africa than in developed countries. The review by Stanifer et al[47] also identified many challenges and limitations, which largely apply to the current study.

The most important aspect in assessing incidence and prevalence of diabetic nephropathy in Africa is currently different diagnostic criteria for CKD. There are no clear definitions on DN. The 2012 KDIGO CKD classification assesses diabetes related kidney changes according to urinary albumin-to-creatinine ratio based on early morning spot urine samples[48]. Quantification of proteinuria in assessing CKD is controversial as no optimal test exists. The National Institute for Health and Clinical Excellence (NICE) guidance has recommended that an early morning urinary ACR should be preferred to other tests of proteinuria, because ACR offers greater sensitivity for the detecting lower, but clinically significant, levels of proteinuria[49]. Almost all the studies included in our review utilized urine tests to diagnose CKD, but only nine studies used ACR. Inconsistencies in the way and manner of reaching a diagnosis of DN in Africans are explained at least in part by issues relating to availability and accessibility of screening or diagnostic tools. Swanepoel et al[50] have reviewed in detail some of the problems associated with nephrology in Africa and discussed the role of lack of amenities in diagnosing renal diseases. Another challenge to making the diagnosis of diabetic nephropathy in Africa is the degree to which other causes of chronic kidney disease have been excluded. A standard armamentarium of tests would include tests looking for HIV, hepatitis B and C, brief collagen screen, syphilis exclusion and other tests would have to be based on history and physical exam.

The classification of CKD is important in the definition of DN and has a few limitations that are universally acknowledged: eGFR underestimates kidney function and there is discordance in the estimates across different estimators[51]; isolated microalbuminuria is a normal feature of aging, inflammation, vascular pathologies, smoking, diet and obesity which are all frequent in diabetes; decline in kidney function is an expected phenomenon with advanced age, just like diabetes risk increases with age. Further considerations to CKD classifications and DN definition limitations is that current guidelines take no notice of the single most important risk factor associated with CKD namely hypertension, which is present in over 50% of people with type 2 diabetes.

Risk factor association was not assessed in 12 of the 32 studies, however common risk factors included were hypertension, raised BMI, HbA1c and duration of diabetes. Despite advances in management over the last three decades, many people with diabetes still develop CKD. This may be partly explained by the poor achievement of blood pressure and blood glucose targets. Recently the JNC 8 guidelines have added to the controversy of various blood pressure targets needed for diabetic patients that would assist in preventing progression to CKD. Optimal targets when reached, however have shown to aid in progression to progression. Another risk factor pertinent to the developing world is the socioeconomic status of individuals in the causative role of diabetic nephropathy. Weil et al[52], in 2010 reviewed factors associated with disadvantage that may increase the risk of diabetic kidney disease, and the barriers to care that hinder attempts to provide an adequate therapeutic response[52].

Several mechanisms underlying the pathogenesis of diabetic nephropathy have been suggested and include glomerular hyperfiltration; hyperglycemia and the increased production of advanced glycation end products; hypoxia-inflammation and the activation of cytokines. Hyperfiltration commonly occur in early in the course of diabetes and involves glucose-dependent dilation of the afferent arteriolar dilation, and the enhanced filtration area secondary to the increase in the number of mesangial cells and capillary loops. Molecular level action involves vasoactive mediators like insulin-like growth factor 1, transforming growth factor beta, nitric oxide, prostaglandin, glucagon and vascular endothelial growth factor[53]. Other hallmarks of diabetic nephropathy include nodular diabetic glomerulosclerosis and diffuse glomerulosclerosis, mediated at least in part by inflammatory processes and immune cells activity[53]. Interstitial fibrosis and tubular atrophy are also seen early in DN, with the underlying pathogenetic mechanism being similar to those in progressive non diabetic renal disease[54].

Diabetic nephropathy ultimately occurs only in susceptible individuals with diabetes; which susceptibility is determined by the combined effect of genetic predisposition and non-genetic factors. Genetic susceptibility to diabetic nephropathy is by nature polygenetic. Whole-genome scanning studies have identified several chromosomal regions linked with diabetic nephropathy; however, the pathophysiologic function of such genetic regions has yet to be fully elucidated. Genetic polymorphisms may explain the familial clustering of diabetic nephropathy[55]. Some studies have suggested some detrimental effect of the double-deletion (DD) polymorphism of the angiotensin-converting enzyme (ACE) genotype on disease progression[56]. Non-genetic determinants of diabetic nephropathy include among others socioeconomic factors, dietary factors, poor hyperglycemic control, hypertension, obesity and early life factors[57,58]. Hypertension appears to be a strong correlate of disease progression in Black people[59,60].

The current review has some limitations. Included studies were mostly based on small samples, with different study designs and most of the studies were cross sectional with only two being retrospective cohorts and one case-control. A large proportion were based in urban clinics with and most of the populations studied were that attending a general diabetic clinic and the results may not be generalizable to primary care populations. Ideally chronic kidney disease should not be diagnosed on the basis of single measurements of serum creatinine and albuminuria, and standard baseline investigations are needed to exclude other causative kidney disease, although there is precedence for this in other studies in the West as well. Finally, detection of microalbuminuria was one the most frequent method to assess the presence of diabetic nephropathy. As microalbuminuria is more a quantitative estimate of endothelial/vascular dysfunction than of diabetic nephropathy, the incidence and prevalence rate of diabetic nephropathy have probably been overestimated when assessing kidney function by urine protein.

In conclusion, the current review gives a small glimpse of the larger numbers of CKD in diabetics in Africa compared to Western society. CKD is a substantial health burden among diabetic patients on the African continent, with prevalence varying from 11% to 83.7% depending on the method of assessment. Estimates suggest that 95% of diabetics may have proteinuria after a 10 years duration of diabetes, about 35% may have an end-stage renal disease after 5 years and 18% die from nephropathy after 20 years of disease duration. Risk factors of CKD include mainly hypertension, obesity, poor glycemic control and disease duration. Better surveillance of diabetes is a necessary first step toward its prevention and control, which is now recognized as an urgent priority. An electronic database in African regions would be ideal to assist in this entity although it is presumed that we are light years away from that. At a primary care level it is very plausible that with early detection, proper screening, and management, the impact of diabetic nephropathy may be better mitigated to lessen its impact on society and healthcare.

COMMENTS
Background

African countries are experiencing an epidemics of diabetes mellitus. Diabetic nephropathy is one the most frequent complications of diabetes mellitus. Several studies on the epidemiology of diabetic nephropathy have been conducted in Africa, but there is no previous published work which synthesizes evidences from this study to provide an overview of the disease on the continent.

Research frontiers

Epidemiological data on diabetic nephropathy in Africa are sparse. These data are important to quantify the magnitude of the disease and assist the formulation of strategies to reduce the impact of nephropathy on people with diabetes in Africa.

Innovations and breakthroughs

This review is the first to synthesize relevant data on diabetic nephropathy in Africa. The authors performed extensive electronic and manual bibliographic searches to determine the prevalence and incidence of diabetic nephropathy on the continent. Although the quality of data was not optimal, estimates suggest that the prevalence of diabetic nephropathy vary between 11%-83.7%. About one third of diabetic patients have end-stage renal disease after 5 years and about one fifth die from nephropathy after 20 years of disease duration. Hypertension, obesity, poor glycemic control and disease duration are the main risk factors of chronic kidney disease among diabetic patients in Africa.

Applications

This review shows that the burden of chronic kidney disease is important among people with diabetes in Africa. The findings will have implications for policy, practice and future research on diabetic nephropathy on the continent.

Terminology

Diabetic nephropathy is an alteration of the function of the kidneys due to diabetes mellitus. It is associated with substantial morbidity and mortality.

Peer-review

The authors of the present manuscript performed extensive electronic and manual bibliographic research to determine the prevalence and incidence of kidney disease in people with diabetes mellitus within countries in Africa. Overall the review is well written.

Footnotes

P- Reviewer: de Oliveira JMF, Laghmani K S- Editor: Ji FF L- Editor: A E- Editor: Zhang DN

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