Sreedhar Mandayam

Dietary protein restriction benefits patients with chronic kidney disease (Review Article)

SUMMARY:  The prevalence of chronic kidney disease (CKD) is rapidly increasing so every strategy should be used to avoid the complications of CKD. Most CKD symptoms or uraemia are caused by protein intolerance; symptoms arise because the patient is unable to excrete metabolic products of dietary protein and the ions contained in protein‐rich foods. Consequently, CKD patients accumulate salt, phosphates, uric acid and many nitrogen‐containing metabolic products, and secondary problems of metabolic acidosis, bone disease and insulin resistance become prominent. These problems can be avoided with dietary planning. Protein‐restricted diets do not produce malnutrition and with these diets even patients with advanced CKD maintain body weight, serum albumin and normal electrolyte values. Non‐compliance is a problem, but this can be detected using standard techniques to provide the patient with appropriate responses. The role of dietary protein restriction in the progression of CKD has not been proven, but it can reduce albuminuria and will prevent uraemic symptoms. Until a means of preventing kidney disease or progression is found, safe methods of management such as dietary manipulation should be available for CKD patients.

Establishing Core Outcome Domains in Hemodialysis: Report of the Standardized Outcomes in Nephrology–Hemodialysis (SONG-HD) Consensus Workshop

Evidence-informed decision making in clinical care and policy in nephrology is undermined by trials that selectively report a large number of heterogeneous outcomes, many of which are not patient centered. The Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) Initiative convened an international consensus workshop on November 7, 2015, to discuss the identification and implementation of a potential core outcome set for all trials in hemodialysis. The purpose of this article is to report qualitative analyses of the workshop discussions, describing the key aspects to consider when establishing core outcomes in trials involving patients on hemodialysis therapy. Key stakeholders including 8 patients/caregivers and 47 health professionals (nephrologists, policymakers, industry, and researchers) attended the workshop. Attendees suggested that identifying core outcomes required equitable stakeholder engagement to ensure relevance across patient populations, flexibility to consider evolving priorities over time, deconstruction of language and meaning for conceptual consistency and clarity, understanding of potential overlap and associations between outcomes, and an assessment of applicability to the range of interventions in hemodialysis. For implementation, they proposed that core outcomes must have simple, inexpensive, and validated outcome measures that could be used in clinical care (quality indicators) and trials (including pragmatic trials) and endorsement by regulatory agencies. Integrating these recommendations may foster acceptance and optimize the uptake and translation of core outcomes in hemodialysis, leading to more informative research, for better treatment and improved patient outcomes.

The mean dietary protein intake at different stages of chronic kidney disease is higher than current guidelines

The actual dietary protein intake of adults without and with different stages of chronic kidney disease is not known. To evaluate this we performed cross-sectional analyses of 16,872 adults (20 years of age and older) participating in the National Health and Nutrition Examination Survey 2001-2008 who completed a dietary interview by stage of kidney disease. Dietary protein intake was assessed from 24-h recall systematically collected using the Automated Multiple Pass Method. Complex survey analyses were used to derive population estimates of dietary protein intake at each stage of chronic kidney disease. Using dietary protein intake of adults without chronic kidney disease as the comparator, and after adjusting for age, the mean dietary protein intake was 1.30 g/kg ideal body weight/day (g/kgIBW/d) and was not different from stage 1 or stage 2 (1.28 and 1.25 g/kgIBW/d, respectively), but was significantly different in stage 3 and stage 4 (1.22 and 1.13 g/kgIBW/d, respectively). These mean values appear to be above the Institute of Medicine requirements for healthy adults and the NKF-KDOQI guidelines for stages 3 and 4 chronic kidney disease. Thus, the mean dietary protein intake is higher than current guidelines, even after adjusting for age.

Comparison of Stage at Diagnosis of Cancer in Patients Who Are on Dialysis versus the General Population

BACKGROUND AND OBJECTIVES Frequent medical encounters in patients with ESRD on dialysis may allow early detection of malignancies despite low rates of cancer screening in this population. It is therefore unclear whether dialysis patients are disadvantaged in terms of cancer diagnosis. This study compared stage at diagnosis of cancer in a population-based sample of patients with ESRD versus the general population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The Surveillance, Epidemiology, and End Results Medicare database was used to identify patients with ESRD and incident cancers from 1992 through 1999. Modified Poisson regression models were used to predict nonlocalized stage of cancer at diagnosis in patients with ESRD versus the general population, adjusting for demographics, cancer site, region, year of diagnosis, and comorbidity. Two general population comparisons were used: Standardized Surveillance, Epidemiology, and End Results public-use data and Medicare control subjects without ESRD matched 3:1 to patients with ESRD. RESULTS A total of 1629 patients with ESRD and incident cancer were identified. Overall, the likelihood of nonlocalized stage at diagnosis was not significantly different for patients with ESRD versus the standardized Surveillance, Epidemiology, and End Results general population or matched Medicare control subjects. Stratifying by cancer site, colorectal cancers were significantly more likely to be diagnosed earlier in the ESRD group, whereas prostate cancers were significantly more likely to be diagnosed at a later stage. CONCLUSIONS With the exception of prostate cancer, patients with ESRD are not more likely to present with later stage malignancies compared with the general population.

Comparison of BMI and anthropometric measures among South Asian Indians using standard and modified criteria

OBJECTIVE To compare the prevalence rates of obesity based on BMI/anthropometric measures, using WHO standard and ethnicity-specific criteria, the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and the International Diabetes Federation (IDF) definitions, among a migrant South Asian Indian population. DESIGN Cross-sectional study conducted in October 2007. SUBJECTS A total of 213 participants of South Asian descent over the age of 18 years. Measures included a questionnaire with basic demographic information and self-reported histories of diabetes, coronary artery disease and/or hypercholesterolaemia. Height, weight, waist and hip circumference and blood pressure measurements were obtained. SETTING Houston and surrounding suburbs. RESULTS WHO-modified (WHO-mod) BMI and IDF waist circumference (WC) criteria independently identified higher numbers of overweight/obese participants; however, when the WHO-mod BMI or IDF WC criteria were applied, nearly 75% of participants were categorized as overweight/obese--a proven risk factor for the future development of metabolic syndrome. CONCLUSIONS Obesity is likely under-diagnosed using the standard WHO and NCEP-ATPIII guidelines. Stressing the use of modified criteria more universally to classify obesity among South Asian Indians may be optimal to identify obesity and help appropriately risk stratify for intervention to prevent chronic diseases.

Dialyzing a patient with human immunodeficiency virus infection: what a nephrologist needs to know.

The percentage of dialysis centers that have reported dialyzing human immunodeficiency virus (HIV)-infected patients increased from 11% in 1985 to 37% in 2000. Being primary care physicians for the dialysis patients, nephrologists are frequently confronted with the management of HIV-infected dialysis patients especially in urban centers. The aims of the present review are to discuss issues that are unique to HIV infection and end-stage renal disease, and to provide dialysis caretakers with sufficient information to help them optimize care and improve outcomes of these patients. Issues related to the choice of renal replacement therapy, vascular access, management of anemia, vaccination, and antiretroviral therapies are discussed in detail.

Comparative outcomes of predominant facility-level use of ferumoxytol versus other intravenous iron formulations in incident hemodialysis patients

BACKGROUND Ferumoxytol was first approved for clinical use in 2009 solely based on data from trial comparisons with oral iron on biochemical anemia efficacy end points. To compare the rates of important patient outcomes (infection, cardiovascular events and death) between facilities predominantly using ferumoxytol versus iron sucrose (IS) or ferric gluconate (FG) in patients with end-stage renal disease (ESRD)-initiating hemodialysis (HD). METHODS Using the United States Renal Data System, we identified all HD facilities that switched (almost) all patients from IS/FG to ferumoxytol (July 2009-December 2011). Each switching facility was matched with three facilities that continued IS/FG use. All incident ESRD patients subsequently initiating HD in these centers were studied and assigned their facility exposure. They were followed for all-cause mortality, cardiovascular hospitalization/death or infectious hospitalization/death. Follow-up ended at kidney transplantation, switch to peritoneal dialysis, transfer to another facility, facility switch to another iron formulation and end of database (31 December 2011). Cox proportional hazards regression was then used to estimate adjusted hazard ratios [HR (95% confidence intervals)]. RESULTS In July 2009-December 2011, 278 HD centers switched to ferumoxytol; 265 units (95.3%) were matched with 3 units each that continued to use IS/FG. Subsequently, 14 206 patients initiated HD, 3752 (26.4%) in ferumoxytol and 10 454 (73.6%) in IS/FG centers; their characteristics were very similar. During 6433 person-years, 1929 all-cause, 726 cardiovascular and 191 infectious deaths occurred. Patients in ferumoxytol (versus IS/FG) facilities experienced similar all-cause [0.95 (0.85-1.07)], cardiovascular [0.99 (0.83-1.19)] and infectious mortality [0.88 (0.61-1.25)]. Among 5513 Medicare (Parts A + B) beneficiaries, cardiovascular events [myocardial infarction, stroke and cardiovascular death; 1.05 (0.79-1.39)] and infectious events [hospitalization/death; 0.96 (0.85-1.08)] did not differ between the iron exposure groups. CONCLUSIONS In incident HD patients, ferumoxytol showed similar short- to mid-term safety profiles with regard to cardiovascular, infectious and mortality outcomes compared with the more commonly used intravenous iron formulations IS and FG.

Primary Care Physician’s Knowledge of Ethnicity-Specific Guidelines for Obesity Diagnosis and Readiness for Obesity Intervention Among South Asian Indians

Many primary care physicians lack sufficient knowledge on current guidelines for overweight/obesity diagnosis among minority groups. We assessed physician knowledge and awareness on modified guidelines for identifying obesity among South Asian Indians (SAIs). Cross sectional survey of 183 physicians practicing in Houston, who reported on their knowledge on guidelines for obesity among SAIs, frequency of measurement of surrogate markers, self-reported competency in management of obesity, and readiness to seek training on obesity diagnosis among SAIs. 65% of physicians agree obesity is a growing problem among SAIs with only 9% of physicians reporting measuring waist circumference. Only 21% of physicians were aware of the recommended WHO modified BMI criteria and 41% the IDF criteria for waist circumference. SAI physicians had significantly higher knowledge compared to other physicians. 78% were ready to seek training on the modified guidelines across ethnicity and training. There is a low level of knowledge on ethnicity-specific guidelines for obesity diagnosis among physicians. There is however a readiness to learn, indicating the need for a physician awareness-training on current obesity guidelines, for various ethnic populations.

Clinical Evidence of Acute Mesoamerican Nephropathy.

Mesoamerican nephropathy (MeN), an epidemic of unexplained kidney disease in Central America, affects mostly young, healthy individuals. Its etiology is a mystery that requires urgent investigation. Largely described as a chronic kidney disease (CKD), no acute clinical scenario has been characterized. An understanding of the early disease process could elucidate an etiology and guide treatment and prevention efforts. We sought to document the earliest clinical signs in patients with suspected MeN in a high-risk population in Nicaragua. Physicians at a local hospital identified suspect cases and documented clinical/laboratory data, demographics, and medical histories. Over a 1-year period, physicians identified 255 mostly young (median 29 years), male (89.5%) patients with elevated creatinine or reduced creatinine clearance. Mean serum creatinine (2.0 ± 0.6 mg/dL) revealed a 2-fold increase from baseline, and half had stage 2 or 3 acute kidney injury. Leukocyturia (98.4%), leukocytosis (81.4%), and neutrophilia (86.2%) predominated. Nausea (59.4%), back pain (57.9%), fever (54.6%), vomiting (50.4%), headache (47.3%), and muscle weakness (45.0%) were common. A typical case of acute MeN presented with elevated (or increased ≥ 0.3 mg/dL or ≥ 1.5-fold from baseline) creatinine, no hypertension or diabetes, leukocyturia, and at least two of fever, nausea or vomiting, back pain, muscle weakness, headache, or leukocytosis and/or neutrophilia. Rapid progression (median 90 days) to CKD was recorded in 8.5% of patients. This evidence can serve as the basis of a sensitive and urgently needed case definition for disease surveillance of early-stage, acute MeN.

Early detection of acute tubulointerstitial nephritis in the genesis of Mesoamerican nephropathy

Mesoamerican nephropathy is a devastating disease of unknown etiology that affects mostly young agricultural workers in Central America. An understanding of the mechanism of injury and the early disease process is urgently needed and will aid in identification of the underlying cause and direct treatment and prevention efforts. We sought to describe the renal pathology in Mesoamerican nephropathy at its earliest clinical appearance in prospectively identified acute case patients in Nicaragua. We considered those with elevated (or increased at least 0.3 mg/dL or 1.5-fold from baseline) serum creatinine, leukocyturia, and either leukocytosis or neutrophilia for inclusion in this biopsy study. Renal tissue was obtained by ultrasound-guided biopsy for examination by light, immunofluorescence, and electron microscopy. All 11 individuals who underwent renal biopsy showed tubulointerstitial nephritis, with varying degrees of inflammation and chronicity. Interstitial cellular infiltrates (predominantly T lymphocytes and monocytes), mostly in the corticomedullary junction; neutrophilic accumulation in the tubular lumens; largely preserved glomeruli; few mild ischemic changes; and no immune deposits were noted. The acute components of tubulointerstitial nephritis were acute tubular cell injury, interstitial edema, and early fibrosis. Chronic tubulointerstitial nephritis included severe tubular atrophy, thickened tubular basement membrane, and interstitial fibrosis. Thus, renal histopathology in Mesoamerican nephropathy reveals primary interstitial disease with intact glomeruli.