Relevance of heat stress and dehydration to chronic kidney disease (CKDu) in Sri Lanka.

Chronic kidney disease in the absence of hypertension and diabetes is a growing problem among agricultural laborers in tropical and subtropical regions. It is unclear if heat stress and dehydration are risk factors for this form of chronic kidney disease (CKDu). To investigate this relationship, agricultural workers in four villages (n = 261) in North Central Province, Sri Lanka completed the US National Institute for Occupational Safety and Health (NIOSH) health hazard evaluation of heat stress, translated into Sinhalese (July 2017). We constructed a heat stress/dehydration index based on the frequency of 16 symptoms (range 0-32; reliability, 0.84). Workers provided a urine sample for dipstick assessment of urine albumin-creatinine ratio (ACR) and refractometer analysis of urine concentration. Of 261 respondents, 41 participants reported diabetes or chronic kidney disease. They scored higher on the heat stress-dehydration index (10.78 vs. 8.03, p < .01) and were more likely to have ACR > 30 (85.4% vs. 69.4%, p < .05). Among 216 non-pregnant agricultural workers without diabetes or kidney disease (mean age, 46.6; 37% male), villagers in the high-CKDu prevalence area were more likely to show signs of dehydration (for example, greater urine concentration, 1.015 vs. 1.012, p < .05, among males); however, the heat stress-dehydration index overall was not associated with ACR or urine concentration. Because an elevated ACR (proteinuria) is not a reliable marker of early CKDu, additional studies are needed to assess the association between heat stress-dehydration symptoms and risk of CKDu.

Glycosylated hemoglobin and the risk of death and cardiovascular mortality in the elderly.

BACKGROUND AND AIMS: Glycosylated hemoglobin (HbA(1c)) has been associated with incident cardiovascular disease (CVD), but the findings are inconsistent. We tested the hypothesis that HbA(1c) may be associated with an increased risk of death and cardiovascular mortality in older adults. METHODS AND RESULTS: We evaluated the association between HbA(1c) with all-cause and cardiovascular mortality in 810 participants without a history of diabetes in a sub-study of the Cardiovascular Health Study (CHS), a community cohort study of individuals > or =65 years of age. Glycosylated hemoglobin was measured at baseline and all-cause and cardiovascular mortality was assessed during the follow-up period. The relation between baseline HbA(1c) and death was evaluated with multivariate Cox proportional hazards regression models. After a median follow-up of 14.2 years, 416 deaths were observed. The crude incidence rates of all-cause mortality across HbA(1c) groups were: 4.4% per year, 4.3% per year and 4.6% per year for tertile 1 (< or =5.6%), tertile 2 (5.61-6.20%) and tertile 3 (> or =6.21%), respectively. In unadjusted and fully adjusted analyses, baseline HbA(1c) was not associated with all-cause mortality and cardiovascular mortality (hazard ratio: 1.16 [95% confidence interval 0.91-1.47] and hazard ratio: 1.31 [95% confidence interval 0.90-1.93], respectively for the highest HbA(1c) tertile compared with the lowest). CONCLUSION: These results suggest that HbA(1c) does not significantly predict all-cause and cardiovascular mortality in non-diabetic community-dwelling older adults.

Kidney function and markers of inflammation in elderly persons without chronic kidney disease: the health, aging, and body composition study.

Inflammatory markers are elevated in persons with estimated glomerular filtration rates less than 60 ml/min/1.73 m2. As cystatin C may detect small changes in kidney function not detected by estimated glomerular filtration rate, we evaluated the association between cystatin C and serum markers of inflammation in older adults with estimated glomerular filtration rate >or=60. This is an analysis using measures from the Health, Aging, and Body Composition Study, a cohort of well-functioning adults aged 70-79 years. Cystatin C correlated with all five inflammatory biomarkers: C-reactive protein (r=0.08), interleukin-6 (r=0.19), tumor necrosis factor alpha (TNF-alpha) (r=0.41), soluble TNF receptor 1 (STNF-R1) (r=0.61), and soluble TNF receptor 2 (STNF-R2) (r=0.54); P<0.0005 for all. In adjusted analyses, cystatin C concentrations appeared to have stronger associations with each biomarker compared with estimated glomerular filtration rate or serum creatinine. Participants with a cystatin C>or=1.0 mg/l had significantly higher levels of all five biomarkers compared to those with a cystatin C<1.0 (mean differences ranging 16-29%, all P<0.05). Cystatin C has a linear association with inflammatory biomarkers in an ambulatory elderly cohort with estimated glomerular filtration rates >or=60; associations are particularly strong with TNF-alpha and the STNF-R.

Lipid modulation in insulin-dependent diabetes mellitus: effect on microvascular outcomes.

Although hyperlipidemia is associated with the development of diabetes complications, the effect of lipid reduction on microvascular complications is unknown. We initiated a 2-year, randomized, double-blinded placebo-controlled pilot trial of simvastatin/diet vs. diet alone in Type 1 diabetic patients without overt nephropathy. Thirty-nine patients with LDL cholesterol 100-160 mg/dl, >10 year duration of diabetes and an albumin excretion rate (AER) <200 microg/min were recruited for study. The primary end-point was change in AER. Secondary end-points were change in ankle-brachial index, progression of retinopathy status, change in vibratory threshold, and development of new clinical neuropathy. Nineteen patients were treated with simvastatin and twenty with placebo. However, because of the lowering of drug initiation levels by the American Diabetes Association, the trial was terminated early with 2 subjects reaching 2 years, 17 reaching 18 months, 36 reaching 1 year, and all 6 months. Simvastatin significantly reduced total cholesterol (mean on treatment 173.4 vs. 191.4, P=.020) and LDL cholesterol (mean on treatment 105.0 vs. 127.7, P<.001). Simvastatin therapy was associated with a slower rise in AER compared to placebo, though the result was not statistically significant (median rate of change/month 0.004 vs. 0.029). There was a trend towards slower progression of neuropathy as measured by vibratory threshold (median change at 1 year 0.03 simvastatin vs. 0.94, P=.07). There was no difference in change in ankle-brachial index, clinical neuropathy status, or retinopathy status. In conclusion, treatment with simvastatin may have a beneficial effect on early nephropathy and diabetic neuropathy, justifying a fully powered trial. However, this would be difficult under current treatment guidelines.

Effect of lipid reduction on the progression of renal disease: a meta-analysis.

BACKGROUND: It has been proposed that hyperlipidemia contributes to the progression of renal disease. A large trial has not been performed; however, a number of small, controlled trials have been reported. We examined the effects of antilipemic agents on glomerular filtration rate and proteinuria or albuminuria in patients with renal disease. METHODS: We used Medline, abstracts from scientific meetings, and bibliographies from recent reviews and scientific reports to locate pertinent studies. Thirteen prospective controlled trials examining the effects of antilipemic agents on renal function, proteinuria, or albuminuria were included. Studies were published as full reports or abstracts and were at least three months in duration. For five of the studies, individual patient data were obtained. Other summary data were independently extracted from the published reports by two investigators and included study quality, subject characteristics, cause of renal disease, change in serum cholesterol, blood pressure, glomerular filtration rate, proteinuria, and albuminuria. RESULTS: There was a lower rate of decline in glomerular filtration rate with treatment compared with controls (treated controls, 0.156 mL/min/month; 95% CI, 0.026 to 0. 285 mL/min/month, P = 0.008). The study results were statistically homogeneous, and in a regression analysis, the effect of treatment on glomerular filtration rate did not correlate with study quality, the percentage change in cholesterol, the type of lipid-lowering agent, or the cause of renal disease. However, longer follow-up correlated with the amount of improvement in glomerular filtration rate from treatment (P = 0.007). There was a tendency for a favorable effect of treatment on protein or albumin excretion [Ln (treatment) - Ln (control) = -0.248, 95% CI, -0.562 to 0.064, P = 0. 077]. However, these results were statistically heterogeneous between studies (P < 0.001). No obvious explanation for this heterogeneity was apparent in a regression analysis examining potential reasons for differences in study results. CONCLUSIONS: Lipid reduction may preserve glomerular filtration rate and may decrease proteinuria in patients with renal disease.

Factors influencing function of temporary dialysis catheters.

AIM: To determine risk factors for failure of temporary dialysis catheters, we prospectively studied the outcome of 178 non-tunneled dual lumen catheters placed in 126 consecutive patients requiring treatment of acute renal failure (ARF) or end-stage renal disease (ESRD). METHODS: Internal jugular (IJ) or subclavian (SC) catheters were used in 122 instances and femoral catheters were employed in 56. RESULTS: IJ or SC catheters with tips in the right atrium or superior vena cava (n = 112) failed (defined as a blood flow < 250 ml/min) 17% of the time, compared with a 40% failure rate for catheters with more peripherally located tips (n = 10), p < 0.05, chi2 testing. In a multivariate analysis, use in ESRD and location peripheral to the SVC were risk factors for catheter failure. Use of one of three catheter brands was associated with a lower failure rate. Although mean venous pressures at 200 ml/min blood flow were higher in IJ or SC catheters that failed, the presence of a high venous pressure, number of catheter uses, IJ vs. SC placement, inpatient vs. outpatient status, and fresh venipuncture vs. placement over a guidewire passed through a previous catheter did not predict catheter malfunction. With femoral catheters, the only risk factor for failure was use in ESRD. CONCLUSION: Of the factors that can be influenced by placement technique, catheter tip location is most important. Whether one catheter brand is superior awaits further confirmation.

Duodenal obstruction in polycystic kidney disease. Case report and review of the literature.

Polycystic kidney disease in a common inherited disorder accounting for 8-10% of cases of end-stage renal disease. The enlarged kidneys often produce pain and hematuria but rarely obstruction of surrounding organs. We report a case of autosomal dominant polycystic kidney disease producing symptomatic duodenal obstruction and malnutrition. Duodenal obstruction should be considered in the differential diagnosis of a patient with polycystic kidney disease and intermittent or persistent nausea and vomiting.

Hyponatremia and hypernatremia.

Hyponatremia and hypernatremia are common electrolyte disorders resulting from disorders in water homeostasis. Hyponatremia usually results from defects in free water excretion, although increased intake may also contribute. The treatment of hyponatremia has been controversial because of the high associated morbidity and mortality and the observation that rapid correction of hyponatremia is associated with the development of central pontine myelinolysis. Mild hyponatremia should be treated with water restriction alone, whereas severe acute or symptomatic hyponatremia should initially be corrected rapidly until symptoms resolve followed by more gradual correction. In all cases, treatment should be individualized on the basis of severity, cause, and duration of the hyponatremia. Hypernatremia results from impaired water ingestion, although increased water losses are often contributory. Hospital-acquired hypernatremia is usually iatrogenic because of inadequate water prescription and is therefore preventable. Hypernatremia is also associated with high morbidity and mortality, both as a result of the underlying disease and inadequate treatment. The primary treatment of hypernatremia is water replacement-repleting water deficits and replacing ongoing losses. Additional treatment should be directed at eliminating excess water losses.

Peritonitis influences mortality in peritoneal dialysis patients.

Mortality remains high in peritoneal dialysis (PD) patients. Known risk factors for mortality include age, diabetes, race, initial albumin level, and cardiovascular disease. Peritonitis is reported to cause death in 1 to 6% of PD patients but has not been well studied as a risk factor for mortality. This study examined 516 adults with a total of 896 yr on PD at one center to determine if peritonitis influenced mortality. Time at risk began on Day 1 of training and ended at death, transplant, or 60 days after transfer to hemodialysis or intermittent peritoneal dialysis. The overall mortality rate was 17.4/100 patient yr. Survival was lower for whites, men, diabetic patients, and older patients. Independent risk factors for mortality (by Cox proportional hazards) were race, diabetes, increased age, and increased peritonitis rate. Use of the Y-set was not associated with decreased mortality. Peritonitis was a risk factor only in whites, nondiabetic patients, and those patients over the age of 60. For every 0.5/yr increase in the peritonitis rate, the risk of death increased 10% in whites, 11% in those patients who were over the age of 60, and 4% for nondiabetic patients. Mortality rates did not decrease over time (1979 to 1995), although peritonitis rates fell significantly (P < 0.001). Rates of Gram-negative and fungal peritonitis showed no trend over time. Peritonitis contributed to 25 of 158 (15.8%) of deaths. Gram-negative/fungal peritonitis accounted for 14 deaths (9.5% of all Gram-negative/fungal episodes) whereas Staphylococcus epidermidis accounted for only 1 death (0.5% of all S. epidermidis episodes) (P < 0.001). Cardiovascular disease was more common in those patients whose deaths were unrelated to peritonitis (P < 0.01), whereas an infectious cause was more common in those patients whose deaths were peritonitis-related (P < 0.001). In this study, peritonitis was a risk factor for death in whites, nondiabetic patients, and older patients. However, the Y-set did not improve survival, perhaps because it does not decrease Gram-negative/fungal peritonitis. To have an impact on survival, efforts are needed to reduce the peritonitis that results from these more serious pathogens.