Efficacy and safety of low-dose heparin in hemodialysis.

INTRODUCTION: The dose of unfractionated heparin (UFH) administered during hemodialysis (HD) varies widely. This prospective study evaluated the safety and efficacy of UFH dose de-escalation. METHODS: Sixty-six prevalent patients on HD receiving UFH per standard-dose protocol (load dose [LD] 50-75 units/kg, maintenance dose [MD] 500-1000 units/hour) had heparin prescription converted to low-dose protocol (start LD 15 units/kg and MD 500 units/hour; dose adjusted in small increments based on assessments of extracorporeal blood circuit). Coagulation parameters, dialysis adequacy, dialyzer clotting, anemia management, and dialyzer reuse rates were compared based on the heparin protocol. FINDINGS: Mean(SD) UFH dose per HD session, before and after protocol conversion, was 6178(2644) and 2913(1116) units, respectively (P < 0.0001). This corresponded to LD 52.1(16.6) units/kg and MD 615(207) units/hour with standard-dose protocol, and LD 18.3(6.5) units/kg and MD 505(27) units/hour with low-dose protocol (P < 0.0001). Mid and postdialysis aPTT was 55.3(31.2) and 35.1(7.8) seconds before, and 37.3(12.9) and 31.5(5.3) seconds after conversion (P = 0.007 and 0.003, respectively); no significant changes in D-dimer levels occurred. Low-dose UFH was associated with a small increase in URR and spKt/V (73.0 and 1.54) compared with dialysis clearance on standard-dose UFH (71.2 and 1.48, respectively, P = 0.02). Weekly dose of ESA decreased by 2388 units postconversion (P = 0.03), while hemoglobin levels and the weekly dose of intravenous iron did not change (P = 0.16 and 0.78). A small rise in the rate of moderate dialyzer clotting at the end of HD was noted with low-dose UFH (5.7% vs. 7.5%, P = 0.002); the rate of severe dialyzer clotting events did not change (P = 0.91). No change in the dialyzer reuse rate was noted (18.5 vs. 17.0 treatments, P = 0.26). DISCUSSION: Low-dose heparinization did not compromise dialysis adequacy and permitted ESA dose reduction. Our findings suggest that in prevalent patients on HD, UFH dose of 15-20 units/kg loading and 500 units/hour maintenance was medically safe and effective.

Longitudinal analysis of one million vital signs in patients in an academic medical center.

BACKGROUND: Recognition of critically abnormal vital signs has been used to identify critically ill patients for activation of rapid response teams. Most studies have only analyzed vital signs obtained at the time of admission. The intent of this study was to examine the association of critical vital signs occurring at any time during the hospitalization with mortality. METHODS: All vital sign measurements were obtained for hospitalizations from January 1, 2008 to June 30, 2009 at a large academic medical center. RESULTS: There were 1.15 million individual vital sign determinations obtained in 42,430 admissions on 27,722 patients. Critical vital signs were defined as a systolic blood pressure <85 mmHg, heart rate >120 bpm, temperature <35°C or >38.9°C, oxygen saturation <91%, respiratory rate ≤ 12 or ≥ 24, and level of consciousness recorded as anything but "alert". The presence of a solitary critically abnormal vital sign was associated with a mortality of 0.92% vs. a mortality of 23.6% for three simultaneous critical vital signs. Of those experiencing three simultaneous critical vital signs, only 25% did so within 24h of admission. The Modified Early Warning Score (MEWS) and VitalPAC Early Warning Score (VIEWS) were validated as good predictors of mortality at any time point during the hospitalization. CONCLUSIONS: The simultaneous presence of three critically abnormal vital signs can occur at any time during the hospital admission and is associated with very high mortality. Early recognition of these events presents an opportunity for decreasing mortality.

Coincident idiopathic focal segmental glomerulosclerosis collapsing variant and diabetic nephropathy in an African American homozygous for MYH9 risk variants.

Familial clustering of disparate kidney diseases including clinically diagnosed hypertensive and diabetic nephropathy, idiopathic focal segmental glomerulosclerosis, and HIV-associated nephropathy are often observed in African Americans. Admixture mapping recently identified the nonmuscle myosin heavy chain 9 gene (MYH9) as a susceptibility factor strongly associated with several nondiabetic etiologies of end-stage renal disease in African Americans, less strongly with diabetes-associated end-stage renal disease. MYH9-associated nephropathies reside in the spectrum of focal segmental glomerulosclerosis/focal global glomerulosclerosis. The renal histology in proteinuric African Americans homozygous for MYH9 risk variants with longstanding type 2 diabetes mellitus is unknown. We report a case of coincident idiopathic focal segmental glomerulosclerosis collapsing variant and diabetic nephropathy in an African American homozygous for the MYH9 E1 risk haplotype. This case demonstrates that diabetic African Americans with overt proteinuria can have mixed renal lesions, including those in the spectrum of MYH9-associated nephropathy. Careful interpretation of kidney biopsies in proteinuric African Americans with diabetes is necessary to exclude coincident nondiabetic forms of nephropathy, precisely define etiologies of kidney disease, and determine the natural history and treatment response in mixed lesions of diabetes-associated and MYH9-associated kidney disease.

Sickle cell trait and development of microvascular complications in diabetes mellitus.

BACKGROUND AND OBJECTIVES: Many African Americans (AA) have both sickle cell trait (SCT) and diabetes mellitus. The objective of this study was to determine whether individuals with diabetes mellitus and SCT have higher rates of microvascular complications relative to those without SCT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective study comparing albuminuria, estimated GFR (eGFR), and microvascular complications in AA with diabetes on the basis of presence of SCT. The study included 821 outpatients who underwent hemoglobin A1c (HbA1c) testing, and presence of SCT was determined using the HbA1c assay. Medical record review and telephone interviews were performed for AA participants. RESULTS: Data were obtained on 376 AA patients (110 with SCT, 245 with neither SCT nor hemoglobin C trait, and 21 with hemoglobin C trait) and 445 European Americans. The mean eGFR and urinary protein excretion were similar between the three AA subgroups. Analysis revealed that 36.3% of AA nontrait and 22.7% of AA SCT participants had retinopathy, peripheral vascular disease, or end-stage kidney disease (P = 0.01). After adjustment for diabetes duration, age, insulin use, and gender, differences in the prevalence of microvascular complications were not observed. CONCLUSIONS: SCT does not increase the risk of microvascular complications in AA with diabetes mellitus.

Distribution of pathologic findings in individuals with nephrotic proteinuria according to serum albumin.

BACKGROUND: Previous studies of the nephrotic syndrome have not carefully examined the relationship between serum albumin and the distribution of pathologic diagnoses found at the time of biopsy. The spectrum of pathologic findings in individuals with nephrotic proteinuria and a normal serum albumin has not been determined. Knowledge regarding the spectrum of findings in nephrotic proteinuria according to serum albumin levels may help nephrologists in the clinical decision making of when to perform a renal biopsy and in determining proper management of these patients. METHODS: Pathologic reports of native kidney biopsies performed for idiopathic proteinuria >3 g/24 h were reviewed. Clinical characteristics and biopsy findings were compared for individuals with serum albumin <30 g/L (Group I), 30 to <35 g/L (Group II) and >/=35 g/L (Group III). RESULTS: There were 57 patients in Group I, 20 in Group II and 35 in Group III. The proportion of individuals with focal and segmental glomerulosclerosis (FSGS) increased according to group: 26% in Group I, 45% in Group II and 74% in Group III. Of 35 patients in Group III, 34 had FSGS or advanced nephrosclerosis from another cause. Seven of 17 Group III patients with follow-up required dialysis after a mean interval of 6 years. Few of these patients received immunosuppressive therapy. CONCLUSIONS: As serum albumin increases in the nephrotic syndrome, the proportion of patients with FSGS increases. Patients with nephrotic proteinuria and a serum albumin >35 g/L suffer from FSGS, nephrosclerosis and have poor renal survival. When evaluating nephrotic patients, nephrologists should use this knowledge about the spectrum of disease in the clinical decision making of when to perform a biopsy and in providing the patient more precise information regarding risks, benefits and alternatives of the kidney biopsy procedure.

Genetic factors in diabetic nephropathy.

Several genes that predispose to type 2 diabetes have recently been identified. In addition to the recognized and powerful effects of environmental factors, there is abundant evidence in support of genetic susceptibility to the microvascular complication of nephropathy in individuals with both type 1 and type 2 diabetes. Familial aggregation of phenotypes such as end-stage renal disease, albuminuria, and chronic kidney disease have routinely been reported in populations throughout the world, and heritability estimates for albuminuria and glomerular filtration rate demonstrate strong contributions of inherited factors. Recent genome-wide linkage scans have identified several chromosomal regions that likely contain diabetic nephropathy susceptibility genes, and association analyses have evaluated positional candidate genes under these linkage peaks. These complimentary approaches have demonstrated that polymorphisms in the carnosinase 1 gene on chromosome 18q, the adiponectin gene on 3q, and the engulfment and cell motility gene on 7p are likely associated with susceptibility to diabetic nephropathy. Additional genes that seem to be of importance in renal phenotypes include manganese superoxide dismutase and angiotensin 1-converting enzyme, with nitric oxide synthase implicated in albuminuria. This article reviews the inherited aspects of diabetic kidney disease with particular emphasis on recently implicated genes and pathways. It seems likely that the risk for diabetes-associated kidney disease is magnified by inheriting risk alleles at several susceptibility loci, in the presence of hyperglycemia.

Nephropathy in siblings of African Americans with overt type 2 diabetic nephropathy.

BACKGROUND: The prevalence of abnormal proteinuria and elevated serum creatinine (sCr) concentrations in diabetic sibs of African Americans (AAs) with overt type 2 diabetic nephropathy (DN) or end-stage renal disease (ESRD) is unknown. METHODS: We measured urine albumin-creatinine (UAC) ratio, sCr, and hemoglobin A1c (HbA1c) in 211 sibs from 66 families (66 unrelated index cases with overt type 2 DN/ESRD, 132 of their diabetic sibs, and 13 of their nondiabetic sibs). Overt DN was defined as a UAC ratio of 1,000 mg/g or greater or ESRD attributed to diabetes. All index cases had at least one diabetic sib screened. RESULTS: Given similar mean ages and body mass indices, nondiabetic sibs had lower UAC ratios and HbA1c values compared with diabetic sibs and index cases (Wilcoxon's rank-sum test, all P < 0.006). More than 60% of index cases had at least one diabetic sib with a UAC ratio of 30 or greater and 300 mg/g or less. Nearly 35% of index cases had at least one sib with a UAC ratio greater than 300 mg/g. Nearly 24% of index cases had at least one sib with an elevated sCr level (> or =1.4 mg/dL [124 micromol/L] in women, > or =1.6 mg/dL [141 micromol/L] in men). CONCLUSION: Asymptomatic elevations in urinary albumin excretion and sCr levels are frequently present in diabetic sibs of AA individuals with overt type 2 DN. Diabetic sibs of AA individuals with type 2 DN should be the focus of intensive screening and intervention programs to slow the current epidemic of diabetic ESRD.