Our population based study is the first to report prevalence and factors associated with CKD from a South Asian country using a locally validated eGFR equation. Our findings indicate a high (12.5%) prevalence of CKD, defined using validated eGFRCKD-EPI(PK) <60 mL/min/1.73 m2, and/or albuminuria ≥3 mg/mmol or higher, among adults aged 40 years or older in Karachi, Pakistan. The prevalence of reduced eGFRCKD-EPI(PK) alone was 5.3% (4.5 – 6.2%). We found that CKD was independently associated with older age, hypertension, diabetes, elevated SBP, raised fasting plasma glucose, raised triglyceride levels, and history of stroke (p < 0.05 for each). Despite a high proportion of associated co-morbidities, CKD remains under-treated with less than 10% and 20% of patients had their BP controlled to targets of ≤130/80 mm Hg, and ≤140/90 mm Hg, respectively per KDIGO 2012 Clinical Practice guidelines . Our results of high prevalence of CKD underscore urgent need for efforts to prioritize CKD on the public health agenda of Pakistan.
The distribution of eGFR in this population illustrate an age related decline, (Figure 1) albeit with relatively well persevered median eGFR among men and women aged 60 years or older . These findings underscore the significance of low eGFR values which should prompt further evaluation even in the elderly in this population.
The high prevalence of CKD is not surprising given the high burden of major CKD risk factors in South Asia. Hypertension and diabetes, both established risk factors for end stage kidney disease, were independently associated with CKD in this population [14, 15]. Results of national surveys indicate that hypertension and diabetes affect about 1 in 3 and 1 in 5 adults, respectively, in Pakistan [16–18]. While, trends data on CKD are not available, the 2010 Global Burden of Disease for Pakistan reported a steep rise in the prevalence of major CKD risk factors during the past two decades [6, 19, 20]. Our finding of high prevalence of CKD is highly suggestive of a parallel increase in the neglected burden of CKD in Pakistan.
We observed that high triglyceride levels were independently associated with CKD. These findings are consistent with those in the Western population demonstrating raised triglycerides in individuals with CKD,  which in part confers increased cardiovascular risk. We also found patients with CKD were more likely to have concomitant stroke (adjusted OR, 95% CI: 1.73 (1.03 – 2.92). A number of studies have established that both reduced eGFR and urine albumin excretion, even in the high normal range, predict a graded increase in cardiovascular morbidity . Furthermore, the adverse environmental exposures including high levels of ambient air pollutants and heavy metals are likely to further enhance the CVD risk associated with CKD in this population . Although lead was phased out of gasoline in Pakistan in 2002, the chronic exposure would predispose this population to lead-related nephrotoxicity especially in the presence of CKD, hypertension or diabetes [23–25].
Recent trials data suggest benefit of lipid lowering on CVD morbidity and mortality among patients with CKD . This practice needs to be integrated into CKD prevention efforts in Pakistan.
We found that BP control was grossly sub-optimal with less than 20% of patients having BP controlled to conventional target of ≤140/90 mm Hg. The recent 2012 KDIGO CKD Clinical Practice guidelines underscore BP target of 130/80 mm Hg or less if the patient has CKD with a higher degree of albuminuria (UACR ≥3 mg/mmol) . Clearly the vast majority of patients with CKD failed to meet even the more relaxed target of ≤140/90 mm Hg in Pakistan (Table 3). These findings call for enhancing provider and patient education regarding importance of BP control among patients with CKD.
Evidence suggests benefit of antihypertensive therapy and blockers of renin-angiotensin system are especially protective in patients with CKD and albuminuria . Strikingly, despite significant co-morbidities among patients with CKD, only 48.3% (95% CI: 42.6 – 54.9%) received antihypertensive medications. Moreover use of blockers of renin-angiotensin system was grossly inadequate with barely 17% of patients taking these nephro-protective agents  (Table 4). Our results highlight the sub-optimal delivery of CKD care in urban Pakistan where private physicians are the dominant source of service provision, and cost of medications is borne out of pocket . Our previous survey of physicians in Pakistan identified serious deficiencies in knowledge and management of hypertension . The situation is likely to be worse for CKD. Studies in the West have shown that screening for CKD can improve BP control among patients recognized to have CKD . Thus, our findings underscore implementation of KDIGO guidelines for screening and management of CKD to be integrated along with management of hypertension and diabetes in the primary health infrastructure in Pakistan, coupled with provider training and public education on awareness of CKD. Appropriate referral mechanism need to be established for those with advanced stages of CKD. Such a model is likely to be cost-effective for prevention of CKD in Pakistan.
Our study has limitations. First, the cross-sectional design of the study does not permit conclusions regarding causation, and reverse causal association of CKD with BP, lipids, and other factors remains a possibility. However, evidence on the importance of controlling raised BP and glucose levels for slowing progression of CKD is well established. Second, since the study was conducted in Karachi, some variation in findings would be expected in other urban and rural areas of Pakistan. However, national survey indicates a high prevalence of hypertension and diabetes across urban and rural Pakistan . Moreover, practices of providers in terms of management of CKD risk factors, and provision of health services in other areas of Pakistan are not better than in Karachi . Thus, prevalence of CKD is also likely to be comparable and our findings generalizable. Third, we relied on single measurement of serum creatinine and UACR, whereas the clinical definition of CKD requires persistent decrease in eGFR or elevation in UACR for at least 3 months. However, single measurement is considered appropriate for epidemiological research, and has been used widely in other studies .
The study has several strengths. This is the first report of prevalence of CKD using a validated eGFR equation with a correction developed in the local South Asian population. Moreover, IDMS (Isotope Dilution Mass Spectrophotometry)-traceable serum creatinine, door to door survey and representative population based on census data of Karachi, and high response rate are the main strength of this study. Thus, our findings would be generalizable to the general population.