High prevalence of undiagnosed chronic kidney disease among at-risk population in Kinshasa, the Democratic Republic of Congo

Chronic Kidney Disease (CKD) is a worldwide health problem [1]. Indeed, the incidence and prevalence of CKD has increased in recent years in both developed and developing countries [2] including in Sub-Saharan Africa (SSA) [3]. In SSA, CKD affects mainly young adults in their productive years and is a significant cause of death [3, 4]. This may occur by death from kidney failure, and also by cardiovascular deaths, which are increased in those with CKD. Major contributory factors for this ominous picture include late referral to hospital, limited renal replacement therapy (RRT), limited capacity of health workers for CKD detection and prevention, and poor awareness of kidney disease in the community [3, 5, 6].

This situation prompted the International Society of Nephrology Commission for the Global Advancement of Nephrology (ISN COMGAN) to make the fight against CKD one of its priorities, by promoting awareness, early detection, and effective treatment [7].

In our recent survey [4] in the general population of Kinshasa, the capital of the Democratic Republic of Congo (DRC) the prevalence of early stage CKD was 10 times greater than that of stage 5 CKD or end stage renal disease (ESRD). Thus, while severe CKD can result in progressive kidney failure, the effects of less-severe CKD are quantitatively more important. Although cumulative evidence shows that early detection and treatment prevents or delays some of its adverse outcomes [8–11], the majority of subjects at early stages of CKD are undiagnosed and under-treated in SSA [6]. Indeed, because of the scarcity of financial resources and shortage of manpower, CKD prevention programs are either rudimentary or virtually nonexistent in the developing world [12].

Furthermore, attention to health problems in SSA is usually been focused on infectious diseases, rather than on chronic non-communicable disease (CND) such as CKD.

Screening of specific groups for CKD, such as those with known diabetes (DM) or with hypertension (HTN), may be more cost effective than screening the general population [13]. But, the benefits of targeted screening of patients with DM and HTN versus screening of general population are debatable [14]. A non validated Modification of Diet in Renal Disease (MDRD) study equation in Black Africans, would probably lead to an over or underestimation of CKD prevalence in Sub-Saharan population.

Nonetheless, since we found an increasing prevalence of CKD risk factors such as HTN, DM, and obesity in Kinshasa [4], along with the co-occurrence of human immunodeficiency virus (HIV) infection and HIV-associated renal diseases [15], it seemed reasonable to target screening on these groups [16]. The objective of this survey was to experiment early detection of a large numbers of previously unidentified persons with or at high risk for CKD. In addition, we determined the prevalence of CKD across selected risk factors and according to the level of kidney function within groups. Finally, socio-demographic features and clinical parameters of this at-risk group were assessed.

This study documents CKD among at-risk population in the health system of Kinshasa, a large city in Sub-Saharan Africa. The overall prevalence of undiagnosed CKD is high, at 36%. This prevalence is probably not real since it was based on non validated MDRD study equation. However, we think that the question of the validity of eGFR MDRD in Black race is debatable. Indeed, since the MDRD Study formula has been adequately validated in African Americans with kidney disease [22], extrapolation to Black Africans may be justified in view of similar genetic and physical attributes. But, validation should still be carried out. Nevertheless, the value of 36% is almost triple the prevalence of CKD in the general population of this city [4]. Similar trend has been noted in the Kidney Early Evaluation Program (KEEP) study [23], mainly for CKD 3+. This fact supports the use of targeted screening in identifying large numbers of subjects at-risk for CKD. It also confirms that the risk factors for CKD that are encountered in developed countries are also found in developing Africa.

In addition, our survey indicates that one person out of five in this group has proteinuria, which was occurred at all stages of CKD. Among individuals classified as having CKD stage 3, 25% had macroproteinuria. As some authors [14, 24, 25] have suggested, those subjects are the groups at most risk for cardiovascular disease (CVD) and CKD progression. With proteinuria and eGFR measurements, we have identify individuals with CKD stage 1 (4% of studied population) and CKD stage 2 (6%). In fact, identifying individuals with these earlier stages is of utmost importance since strong evidence emerge that the renal and cardiovascular risks that are associated with stage 1 and 2 are nearly equal to those of stage 3 [14]. Regrettably, in spite of this prevalence of proteinuria, in most cases it was neither detected earlier nor correctly managed before this study was done. Indeed, in almost all centres, 24 hour-quantitative proteinuria or dipstick proteinuria were not routinely available outside this study. Qualitative proteinuria was carried out in usual practice using the acetic acid method, which has limits of sensitivity and specificity [26]. Furthermore, and until now, in ordinary secondary care in Kinshasa, renal complications are assessed only by serum creatinine alone instead of resorting to formula -based estimates of creatinine clearance or eGFR. Consequently, many cases of CKD could be missed by using the serum creatinine alone.

In this present study, we found a discrepancy between prevalence of dipstick positive protein and proteinuria mainly in CKD stage 3. This difference may be due to the fact that only patients with dipstick positive protein 3+ were tested for 24-hour proteinuria. It also confirms differences in sensitivity and specificity between tests as reported recently by Konta et al. [27]. In their survey, the authors have demonstrated that dipstick positive proteins are more indicative of microalbuminuria than macroalbuminuria.

However, despite the fact that dipstick proteinuria has limited diagnostic value, it is of a great prognostic value. Indeed, dipstick positive protein has been associated with increased risk of cardiovascular events, including the development of HTN [28], DM [29], and ESRD [30]. But not all studies are in agreement [31] and it is unclear whether microalbuminuria is a marker of kidney disease or generalized vascular disease [32].

As expected [33], HTN, DM and proteinuria were independently associated with CKD 3+. Inadequate BP and/or poor glucose control may explain the CKD that we observed. The lack of BP control shown in our patients with HTN, of whom 78% were uncontrolled, is a bit higher than the 73% seen in Americans [34]. In addition, only 6% of participants with HTN and 4% of patients with DM and HTN having CKD had their BP controlled to the JNC VII recommended level of less than 130/80 mmHg [18]. This level of control is lower than the 20% in the New Opportunities for Early Renal Intervention by Computerised Assessment study (NEOERICA) [35] and the 11% reported in the National Health and Nutrition Examination Survey (NHANES III) [34]. It highlights the inadequate levels of BP control in this screening population, placing them at risk for cardiovascular and/or renal events, particularly ESRD [8] and may thereby increase medical care costs. Only 23% of all studied population received treatment to block the renin-angiotensin system. Certainly, ACEI may be less effective in Blacks, in whom the incidence of high renin hypertension is lower than in Caucasian population. However, the African-American Study of Kidney Disease and Hypertension (AASK) confirmed the reno-protective effects of ACEI compared to calcium blocker in Blacks with hypertensive nephropathy [36]. Also, in this AASK trial [36], an average of 2.6 drugs was needed to achieve BP goals, while the average number of drugs used by patients with HTN in the present survey was 1.3.

However, a secondary analysis of AASK study [37] comparing ACEI versus β blocker and Calcium blocker versus β blocker have shown that BP control does not always prevent progression of renal failure. These findings suggest that factors other than BP elevation likely participate in the progression of ''hypertensive" nephrosclerosis. But, we note that in this study [37], the authors did not test the hypothesis that treatment versus no treatment of HTN preserves kidney function. The bulk of evidence shows that BP control slows the progression of hypertensive kidney diseases, and control of the BP is not good in Kinshasa.

HTN was also common with type 2 diabetes, which was more frequent than type 1 in the present study. In addition, most patients with DM in this study had poor glucose control. Appropriate management of DM and HTN are important to both the prevention and control of renal disease [23]. Awareness by patient and health care provider will help in this regard, and our study has advanced that awareness in Kinshasa.

Age and duration of DM also influenced the occurrence of CKD in this present study.

Duration of DM is well recognized as an important risk factor for diabetic nephropathy [9]. But duration of HTN did not have a correlation with low eGFR in this survey. That fits well with the fact that in most cases of renal diseases, HTN is the result of, rather than the cause of, the low eGFR. However, we do not know the exact causes of low eGFR in the subjects of this study.

CKD can also result from transmissible diseases such as HIV infection. Our observations show that the prevalence of CKD among HIV positive people is 12%. This value is lower than the 20% found in Uganda [38] and the 27% reported in Soweto [39]. It is on the other hand higher than the 2% [40] and 0.7% [41] described in the USA and in Ethiopia, respectively. This discrepancy of prevalence between these studies could be due to the difference in methodology applied in each survey. It could also reflect an ethnic disparity [42], or even a socio-economic gradient. But, it is hard to determine the true CKD prevalence among HIV population because a validated eGFR method does not exist in HIV subjects.

Among patients with a family history of kidney disease, the proportion of CKD was 8%. In addition, while Ramirez et al [43] showed that FH-KD was a strong determinant of proteinuria, with OR of 2.5, FH-KD in our survey was not associated with proteinuria or with reduction of kidney function. This observation may due to low awareness of CKD and its familial associations by both health workers and the lay population.

Another preventable risk factor for CKD is the use of herbal remedies, which was found in our study in univariate analysis but not in multivariate analysis. Others have reported renal toxicity and other adverse effects of traditional herbal remedies [44]. We can not state which of the remedies are nephrotoxic since studies of their composition are lacking.

Some risk factors for CKD such as smoking or LBW, reported elsewhere [43], were not observed in the present study. However, most of our study population did not have birth certificates or knowledge of their weight at birth, so the risk of LBW is probably not adequately assessed in this study. The reason why tobacco use was not associated with proteinuria remains unclear and deserves further attention.

An important issue that is not resolved by this study is how to reach high-risk individuals who do not attend these clinics as well the problem of payment for antihypertensive and antidiabetic drugs.

We think that our recent model of annual screening for proteinuria and CKD risk factors [45] combining educational message, detection and management of risk factor in general population may contribute partly to reach this first goal.

However, despite their benefits, treatments of HTN and/or DM are costly. This limits their use in SSA, where about half the population lives on less than $ 1 per day [3]. In Kinshasa the annual cost of drugs for optimal antihypertensives such as thiazide diuretics, calcium blocker, or ACE inhibitors, ranges from US $ 100, $ 250, and $ 1000 per patient, respectively, as estimated from a weighted average of wholesale prices for five proprietary products in the market. In this city, it is currently estimated that there are 2.8 million hypertensives [4]. Thus, if all hypertensives were treated with one or more of these drugs we can project that annual cost for these drugs would be between $ 280 million and $ 2.8 billion. If the same drugs are used in combination, the cost of the treatment would be even higher. In patients with DM, the estimated cost per patient of oral antidiabetics and insulin are about $ 200 and $ 350 per year, respectively. If we extrapolate these figures to the current 1.2 million diabetics in Kinshasa [4], the annual cost is over $ 240 million for biguanide-metformin and $ 420 million for insulin. The expenditure in patients with DM and HTN would be even higher. On the assumption that 1% of the hypertensive or diabetic population would evolve to ESRD there would be 28,000 hypertensives and 12,000 diabetics requiring RRT. Hence, we can project the annual cost for RRT in Kinshasa at ~$1.4 billion for peritoneal dialysis or ~2.5 billion for hemodialysis. These estimates for the cost of RRT will be higher if more hypertensives and/or diabetics progress to ESRD. It is clear that long-term dialysis will not be an option for most Africans with renal failure, and it is also likely that the use of anti-hypertensives and better treatment for DM will only reduce, not eliminate, the number of cases of diabetic and hypertensive nephropathy that evolve to ESRD. That said, the increased use of anti-hypertensives and better treatments for DM may reduce non-renal morbidity and mortality, which may make these treatments worth their expense. Indeed, El-Nahas [1] has made a case for the cost-effectiveness of screening for CKD, worldwide, in all populations.

We believe that use of anti-hypertensives and anti-diabetic treatment will reduce morbidity and mortality, but the magnitude of this benefit is not known. Still, in consideration of the combined cost of anti-hypertensive and diabetic treatment, as compared to the expense of cardiovascular disease and chronic dialysis, the cost of anti-hypertensive and diabetic treatment is cheaper. Thus, we need the support of the pharmaceutical industry as well as community support to supply developing countries with necessary renoprotective and cardioprotective drugs.

Furthermore, it is noteworthy that this study population has a very different age distribution from that of the DRC in general, the subjects of this study having an older age than that of the general population of Kinshasa. This could suggest that there will be an increasing number of such at-risk subjects in the near future. Hence, this situation is likely to worsen over the next 20 years if no effective preventive measures are taken.

All health care workers will need to be engaged in this effort. It is impossible that a few nephrologists would be able to implement detection and prevention of CKD for the whole city, let alone the entire DRC. Indeed, in 2004, the DRC counted only 0.11 physicians per 1000 population and 0.52 nurses per 1000 population [46]. Consequently, management of the patients in this country must be by nurses for primary care and by general practitioners for secondary care. Adapting K/DOQI guidelines must account for local conditions and manpower.

Despite the above limitations, our findings show the effectiveness of community based targeted health screening program, in identifying significant numbers of persons with CKD previously undiagnosed, and also in finding those with inadequate risk-factor control. This study suggests that there is a great potential for decreasing CKD as well as ESRD incidence and cardiovascular morbidity or mortality by optimizing modifiable risk factors in this high-risk population. It also suggests that the costs of treating those with CKD may be cost-beneficial, by averting the morbidity of cardiovascular disease and also the very high cost of RRT. Furthermore, our study emphasizes the urgent need for increased training of generalist physicians and nurses in CKD prevention programs as well an active collaboration between traditional health care and nephrology services.

The establishment of prevention programs in developing countries is also a political and financial challenge. This challenge could be taken up by creation of international funding assistance as exists for HIV or tuberculosis infection, the goal of which would be to support the program of prevention of CKD, and some of its risk factors such as HTN, DM and obesity.

Finally, further study is needed to improve the precision of these preliminary data and to assess the benefit of antihypertensive such as ACEI on the progression of renal disease in Black Africans. That is because studies in Afro-Americans may probably not be directly applicable to Sub-Saharan Africans and extrapolation must be made with caution.