This Month in AJKD

CKD in China: Prevalence and Risk Factors 

See Zhang et al, pages 373-384 and Stevens et al, pages 353-357.

China, with a population of over 1.3 billion people and making up almost 20% of the world’s total population, is the most populous country in the world. As chronic kidney disease (CKD) is a growing public health burden worldwide, it is crucial to understand its impact in this large and developing country. As a part of AJKD’s World Kidney Day issue, Zhang et al report the prevalence of CKD and risk factors for development and progression of kidney disease in a representative survey of 14,000 adults in Beijing, China’s capital city. They found a CKD prevalence of 13% (95% CI, 11.9 to 14.2), corresponding to 1.43 million adults. The authors also determined a number of factors independently associated with reduced kidney function in this population, including older age, use of nephrotoxic medications, living in a rural area, history of cardiovascular disease, reduced high-density lipoprotein cholesterol levels, and presence of hypertension. In a related editorial, Stevens et al compare the results to recent estimates in the US, and call attention to the high prevalence of CKD in the elderly.

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Cystatin C Levels in the US and New GFR Estimating Equations Using Cystatin C 

See Köttgen et al, pages 385-394; Stevens et al, pages 395-406; and Shlipak, pages 358-361.

Serum cystatin C has garnered increasing attention as a potentially useful filtration marker for estimating kidney function, as previous reports have noted that cystatin C is not affected by muscle mass. However, its use to date has chiefly been limited to research studies. In this issue, 2 important studies attempt to clarify the role of cystatin C in estimating glomerular filtration rate (GFR). Köttgen et al examined data from NHANES III and found that cystatin C levels were higher in men compared to women, whites compared to blacks and Hispanics, and older compared to younger people. Serum cystatin C was >1.12 mg/L in 1% of nondiabetic, nonhypertensive people aged 20-39 years, as compared to >50% of people over 80 years in age.

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Stevens et al developed GFR estimating equations in populations with chronic kidney disease (CKD) using cystatin C alone; cystatin C with age, sex, and race; creatinine with age, sex, and race; and both cystatin C and creatinine with age, sex, and race. The percent of GFR estimates within 30% of the measured GFR for the 4 equations was 82%, 84%, 85%, and 89%, respectively. They also found that age, sex, and race influenced the association of cystatin C to GFR, albeit to a smaller extent than for creatinine and GFR. Using the equation based on cystatin C alone, the serum levels of cystatin C corresponding to estimated GFR levels of 45, 60, 75, and 90 mL/min/1.73 m2 are 1.57, 1.23, 1.02 and 0.88 mg/L, respectively. Taken together, these 2 studies suggest that serum cystatin C is affected by factors other than GFR. An editorial by Dr Shlipak discusses the implications of GFR estimation using cystatin C in populations with and without CKD, specifically citing literature that shows stronger associations in the elderly between cystatin C and adverse outcomes than creatinine and outcomes. He addresses the need for further research to fully determine the burden of CKD in the elderly and the value of interventions to reduce the risk of incident CKD.

Multifactorial Interventions to Prevent Diabetic Complications: A Quality Improvement Report 

See Senior et al, pages 425-434.

While clinical trials have shown that multifactorial interventions can prevent micro- and macro-vascular complications of diabetes, implementing these interventions in less densely populated areas can be a unique challenge. In this issue, Senior et al sent teams of nurses and dieticians to 2 urban and 3 rural areas in Northern Alberta, Canada to provide care for 424 individuals with diabetes and hypertension or albuminuria. Mean blood pressure, hemoglobin A1c, and low-density lipoprotein cholesterol all significantly improved during follow-up (133/74 versus 129/71 mm Hg, 8.1 versus 7.5%, 104 versus 93 mg/dL, respectively [P <0.001 for all]) while there was no increase in weight. In addition, the proportion of patients prescribed recommended therapies (eg, angiotensin-converting enzyme inhibitors and lipid lowering and antiplatelet therapy) increased from 37.0% to 60.1% (P <0.001). They concluded that delivery of multifactorial interventions by nurse/dietitian teams in a rural community setting was feasible; future research is required to assess the cost associated with this intervention and potential cardiovascular and mortality benefits.

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Sevelamer Versus Calcium-Based Phosphate Binders: A Secondary Analysis of the DCOR Trial 

See St. Peter et al, pages 445-454 and Winkelmayer and Tonelli, pages 362-365.

The ideal composition of phosphate binders to reduce mortality and morbidity in dialysis patients is hotly debated. The recent Dialysis Clinical Outcomes Revisited (DCOR) trial compared the effects of sevelamer with calcium-based phosphate binders on mortality and hospitalization in hemodialysis patients. Unfortunately, many patients were lost to follow-up, precluding an intention-to-treat analysis in the original publication. In this issue, St. Peter et al report the results of a pre-planned intention-to-treat analysis, using data from the Centers for Medicare & Medicaid Services for ascertainment of survival. They found that all-cause and cardiovascular mortality did not differ significantly between treatment groups, confirming the results of the original analysis. The authors do note that the all-cause hospitalization rate and number of hospital days were lower in the sevelamer group. In an accompanying editorial, Winkelmayer and Tonelli compare the St. Peter et al secondary analysis with the original DCOR publication by Suki et al, focusing on the subgroup analyses and adjustment for multiple testing. The editorialists discuss the importance of interpretation of secondary analyses, given the potentially large impact of these trials on treatment and prescriptions.

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Association of Diarrhea With Graft Loss and Mortality 

See Bunnapradist et al, pages 478-486.

Diarrhea is a common complication following kidney transplantation and has numerous potential etiologies. Diarrhea is associated with worse graft outcomes, but the risk factors for diarrhea and the magnitude of its association with graft lost and death is still unclear. In this issue, Bunnapradist et al examined 41,442 first kidney transplant recipients in the United States from 1995 to 2002 and used claims data to assess causes of diarrhea. The 3-year cumulative incidence of diarrhea was 22%, and the most common diagnosis, in 18%, was noninfectious diarrhea of unspecified cause. Women, patients with type 1 diabetes, and patients on regimens containing tacrolimus and mycophenolate mofetil had a significantly increased risk of noninfectious diarrhea. Critically, unspecified noninfectious diarrhea was associated with increased risk of both graft failure (HR, 2.13; 95% CI, 1.98 to 2.28) and patient death (HR, 2.04; 95% CI, 1.85 to 2.24).

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