Comparison of Dialysis Unit and Home Blood Pressures: An Observational Cohort Study.

RATIONALE & OBJECTIVE: Prior studies of patients receiving maintenance hemodialysis have shown that, on average, blood pressure (BP) measured predialysis is higher than BP measured at home. We hypothesized that a subset of hemodialysis patients has BP that is higher when measured at home than when measured predialysis and this subgroup of patients has a higher prevalence of left ventricular hypertrophy. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 97 hypertensive hemodialysis patients enrolled in the Blood Pressure in Dialysis Study (BID), a randomized trial of comparing target predialysis BP ≤140/90 to 155-165/90 mm Hg. EXPOSURE: Differences between predialysis and next-day home systolic BP measured ≥6 times over 1 year. OUTCOME: Left ventricular mass index (LVMI) by cardiac magnetic resonance imaging. ANALYTICAL APPROACH: A hierarchical clustering analysis divided patients into 3 clusters based on the average and variability of differences in systolic predialysis and home BP. Clusters were compared with respect to clinical factors and LVMI. RESULTS: Mean differences between predialysis and home systolic BP were 19.1 (95% CI, 17.0 to 21.1) mm Hg for cluster 1 ("home lower"), 3.7 (95% CI, 1.6 to 5.8) mm Hg for cluster 2 ("home and predialysis similar"), and -9.7 (95% CI, -12.0 to -7.4) mm Hg for cluster 3 ("home higher"). Systolic BP declined during dialysis in clusters 1 and 2 but increased in cluster 3. Interdialytic weight gains did not differ. After adjusting for sex and treatment arm, LVMI was higher in cluster 3 than in clusters 1 and 2: differences in means of 10.6 ± 4.96 (SE) g/m2 (P = 0.04) and 12.0 ± 5.08 g/m2 (P = 0.02), respectively. LIMITATIONS: Limited statistical power. CONCLUSIONS: Nearly one-third of participants had home BPs higher than predialysis BPs. These patients had LVMI higher than those with similar or lower BPs at home, indicating that their BP may have been undertreated.

Eosinophilia and risk of incident end stage kidney disease.

BACKGROUND: Eosinophils in kidney disease are poorly understood and are often incidental findings on kidney biopsy. Eosinophilia in blood and renal biopsy tissue is associated with a host of immune and non-immune kidney diseases. The significance of eosinophilia in renal diseases has not been well addressed. We evaluated the presence of peripheral eosinophilia (> 4% of blood leukocytes) with biopsy tissue eosinophilia and their association with end-stage-kidney-disease (ESKD). METHODS: A nested case-control (2:1) of patients who underwent kidney biopsies at Johns Hopkins Hospital and Medical University of South Carolina from 2004 to 2018 were included in the study. From the 616 eligible patients, 178 patients were identified through the registry of kidney biopsies as 18 years or older without missing biopsy reports or hematology results. Controls (n = 154) had no ESKD at the time of case (n = 24) designation and were assembled using incident density sampling and matched on age and sex. The association of peripheral eosinophilia (> 4% of peripheral blood leukocytes) with the risk of progression to ESKD was evaluated using conditional logistic model after adjusting for clinical demographics. RESULTS: Among 178 patients, 65 (37%) had peripheral eosinophilia and 113 (63%) had no eosinophilia. Compared to patients without eosinophilia, patients with peripheral eosinophilia were notably male and had a higher serum creatinine at the time of their biopsy. Peripheral eosinophilia was associated with higher risk of ESKD (OR 15.9 [1.9, 134.7]) adjusted for patient demographics including hypertension, proteinuria and eGFR at the time of kidney biopsy. Peripheral eosinophilia had a significant linear association with kidney tissue eosinophils, 22 (standard deviation [SD] 20) per high power field (hpf) in 4-10% peripheral eosinophilia, 19 (SD 18) per hpf in ≥10% eosinophilia and 3 (SD 7) per hpf in no eosinophilia (P <  0.001). CONCLUSIONS: Peripheral eosinophilia is an independent predictor of tissue eosinophilia and subsequent progression to ESKD. Peripheral eosinophilia may be an early biomarker for underlying inflammation and disease, but further studies to investigate this clinical association are warranted.

Diffuse membranoproliferative glomerulonephritis with focal sclerosis and renal amyloidosis in an adult male with autosomal dominant dystrophic epidermolysis bullosa: a case report.

Previous reports of glomerular disease in adult patients with autosomal dominant dystrophic epidermolysis bullosa (EB) are limited and include post-infectious glomerulonephritis, IgA nephropathy, amyloidosis, and leukocytoclastic vasculitis. To our knowledge, membranoproliferative glomerulonephritis (MPGN) has not been described before. We report a case of a 39-year-old male with autosomal dominant dystrophic EB, presenting with bilateral leg swelling of one-week duration. There was no other significant past medical history. The physical examination was remarkable for scars and erosions over all body areas, with all extremities with blisters and ulcers covered, absent finger and toenails and bilateral lower extremity edema. Serum creatinine was 0.9 mg/dL, albumin 1.3 g/dL and urine protein excretion 3.7 g/24 h. Viral markers (hepatitis-B, C, and HIV), complement c3 and c4 levels and auto-immune antibody profile all remained negative or within normal limits. Renal ultrasound and echocardiogram were normal. Renal biopsy recovered 14 glomeruli, all with proliferation of mesangial and endothelial cells as well as an expansion of the mesangial matrix, focal segmental sclerosis and amorphous homogeneous deposits demonstrating apple-green birefringence under polarized light with Congo red stain. Our observation emphasizes the importance of recognizing MPGN and secondary amyloidosis in patients with EB, especially with the availability of newer treatment modalities.

Prevalence of CKD, Diabetes, and Hypertension in Rural Tanzania.

INTRODUCTION: Chronic kidney disease (CKD), diabetes, and hypertension play a disproportionate role in the growing public health challenge posed by noncommunicable diseases (NCDs) in East Africa. The impact of these NCDs may pose the greatest challenge in rural areas with limited screening and treatment facilities, although precise prevalence estimates of these conditions in rural Tanzania are lacking. METHODS: The prevalence of CKD, diabetes, and hypertension, were estimated from a probability sample of adults (n = 739) residing in 2 communities within Kisarawe, a rural district of Tanzania. Following consent, participants were studied in their homes. Random point-of-care (POC) measures of glycosylated hemoglobin and blood pressure, were obtained. Serum creatinine, drawn at the POC and measured at Muhimbili National University, was used to calculate estimated glomerular filtration rate with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS: The median age was 35 years (interquartile range 25-45 years). Overall the pooled prevalence for CKD stages III, IV, and V was 12.4% (95% confidence interval [CI] = 10.2-14.8). Surprisingly, the prevalence of CKD stage V (3.0%; 95% CI = 2.1-4.4) was high among the youngest age group (18-36 years). The prevalence estimates for prehypertension and hypertension were 38.0% (95% CI = 34.6-41.5) and 19.9% (95% CI = 17.1-22.9), respectively. The prevalence estimates for prediabetes and diabetes were 25.7% (95% CI = 22.6-29.1) and 14.8% (95% CI = 12.4-17.6), respectively. CONCLUSION: Although this pilot study had a relatively small sample size, the prevalence estimates for CKD, diabetes, and hypertension were higher than we expected based on previous estimates from Tanzania. CKD was not significantly associated with diabetes or hypertension, suggesting the possibility of an alternative causality.

BP in Dialysis: Results of a Pilot Study.

The optimal BP target for patients receiving hemodialysis is unknown. We randomized 126 hypertensive patients on hemodialysis to a standardized predialysis systolic BP of 110-140 mmHg (intensive arm) or 155-165 mmHg (standard arm). The primary objectives were to assess feasibility and safety and inform the design of a full-scale trial. A secondary objective was to assess changes in left ventricular mass. Median follow-up was 365 days. In the standard arm, the 2-week moving average systolic BP did not change significantly during the intervention period, but in the intensive arm, systolic BP decreased from 160 mmHg at baseline to 143 mmHg at 4.5 months. From months 4-12, the mean separation in systolic BP between arms was 12.9 mmHg. Four deaths occurred in the intensive arm and one death occurred in the standard arm. The incidence rate ratios for the intensive compared with the standard arm (95% confidence intervals) were 1.18 (0.40 to 3.33), 1.61 (0.87 to 2.97), and 3.09 (0.96 to 8.78) for major adverse cardiovascular events, hospitalizations, and vascular access thrombosis, respectively. The intensive and standard arms had similar median changes (95% confidence intervals) in left ventricular mass of -0.84 (-17.1 to 10.0) g and 1.4 (-11.6 to 10.4) g, respectively. Although we identified a possible safety signal, the small size and short duration of the trial prevent definitive conclusions. Considering the high risk for major adverse cardiovascular events in patients receiving hemodialysis, a full-scale trial is needed to assess potential benefits of intensive hypertension control in this population.

Dyshomeostasis of serum sodium concentration in congestive heart failure.

Congestive heart failure (CHF) is the most common discharge diagnosis in the United States and accounts for greater than 1 million hospital discharges annually. CHF is associated with many serum electrolyte abnormalities, the most common and perhaps most significant of which is hyponatremia. CHF with hyponatremia makes the already high morbidity and mortality of CHF even more unfavorable. Further, the usual treatment for CHF with diuretics usually aggravates hyponatremia. Hyponatremia may result in impaired cognition and neurologic performance in a large number of patients, which is usually reversible with correction. The high morbidity and mortality with CHF and hyponatremia are not improved with the usual treatment with diuretics or ultrafiltration. This article provides an overview of the pathophysiology of hyponatremia in CHF. In addition, the authors will explore the various treatment options that are available and the evidence to support their utility.

Does poly-N-acetyl glucosamine patch use reduce arteriovenous fistula and graft failure rates in hemodialysis patients with end-stage renal disease?

BACKGROUND: Maintenance of functional vascular access is crucial for the delivery of hemodialysis. The SyvekPatch is a topical marine microalgal poly-N-acetyl glucosamine hemostat approved by the Food and Drug Administration for use in the local management of bleeding wounds, such as vascular site, percutaneous catheters or tubes, and surgical debridement. METHODS: The Preservation of Vascular Access Study was designed to investigate the effectiveness of patch use in reducing failure rates of arteriovenous fistulas or grafts. Data from medical records of patients who received hemodialysis from January 2001 to December 2005 at local ambulatory outpatient hemodialysis units in Charleston, South Carolina were analyzed. To explore whether greater use of the poly-N-acetyl glucosamine patch resulted in more favorable outcomes, patients were categorized into no patch use (n = 183) or 2 groups involving patch use, <70% of hemodialysis sessions (n = 88) or >or=70% of hemodialysis sessions (n = 64). The outcome measure was failure of access site estimated using Poisson regression models. RESULTS: Three hundred thirty-five patients (54% women) with 178 fistulas (44%) and 227 grafts (56%) were included. The study population was predominantly African American (84%), with a median age of 58 years. The adjusted relative rate of access failure involving patch use in <70% of hemodialysis sessions versus no patch use was 0.84 (95% CI, 0.37-1.94), and for patch use in >or=70% of hemodialysis sessions versus no patch use was 0.40 (95% CI, 0.16-1.02; trend P = 0.045). CONCLUSIONS: The Preservation of Vascular Access Study results are consistent with improved access survival with frequent patch use. The application of patch in this population is a simple, well-accepted intervention and warrants further investigation.

Blockade of renal medullary bradykinin B2 receptors increases tubular sodium reabsorption in rats fed a normal-salt diet.

The present study was performed to test the hypothesis that under normal physiological conditions and/or during augmentation of kinin levels, intrarenal kinins act on medullary bradykinin B(2) (BKB(2)) receptors to acutely increase papillary blood flow (PBF) and therefore Na(+) excretion. We determined the effect of acute inner medullary interstitial (IMI) BKB(2) receptor blockade on renal hemodynamics and excretory function in rats fed either a normal (0.23%)- or a low (0.08%)-NaCl diet. For each NaCl diet, two groups of rats were studied. Baseline renal hemodynamic and excretory function were determined during IMI infusion of 0.9% NaCl into the left kidney. The infusion was then either changed to HOE-140 (100 microg.kg(-1).h(-1), treated group) or maintained with 0.9% NaCl (time control group), and the parameters were again determined. In rats fed a normal-salt diet, HOE-140 infusion decreased left kidney Na(+) excretion (urinary Na(+) extraction rate) and fractional Na(+) excretion by 40 +/- 5% and 40 +/- 4%, respectively (P < 0.01), but did not alter glomerular filtration rate, inner medullary blood flow (PBF), or cortical blood flow. In rats fed a low-salt diet, HOE-140 infusion did not alter renal regional hemodynamics or excretory function. We conclude that in rats fed a normal-salt diet, kinins act tonically via medullary BKB(2) receptors to increase Na(+) excretion independent of changes in inner medullary blood flow.

Effect of low environmental salinity on plasma composition and renal function of the Atlantic stingray, a euryhaline elasmobranch.

Marine elasmobranchs maintain internal osmolality higher than their external environment, resulting in an osmotic gradient for branchial water uptake. This gradient is markedly increased in low-salinity habitats. The subsequent increase in water uptake presents a challenge to volume homeostasis. The Atlantic stingray is a marine elasmobranch that inhabits a remarkable range of environmental salinities. We hypothesized that the ability of these stingrays to regulate fluid volume in low-salinity environments is due primarily to a renal glomerular and tubular functional reserve. We tested this hypothesis by measuring renal excretory function after a rapid and sustained 50% reduction in the osmolality of the external medium. Atlantic stingrays were maintained in harbor water [control salinity (CS) approximately 850 mosmol/kgH(2)O] for 1 wk. Rays were then either transferred to diluted harbor water [low salinity (LS) approximately 440 mosmol/kgH(2)O] or maintained in CS for a further 24 h. Renal excretory function was markedly higher in the rays subjected to low salinity. Glomerular filtration rate was threefold higher and urine flow rate ninefold higher in the LS group. The clearance of solute-free water was greater, and solute-free water comprised a significantly larger proportion of the urine output for the stingrays transferred to dilute harbor water. We conclude that 1) the kidneys of Atlantic stingrays have a remarkable glomerular and tubular functional reserve, and 2) the marked increase in renal function attenuates the increase in fluid volume when these fish move into low-salinity habitats.

Cloning and functional characterization of a second urea transporter from the kidney of the Atlantic stingray, Dasyatis sabina.

The cloning of cDNAs encoding facilitated urea transporters (UTs) from the kidneys of the elasmobranchs indicates that in these fish renal urea reabsorption occurs, at least in part, by passive processes. The previously described elasmobranch urea transporter clones from shark (shUT) and stingray (strUT-1) differ from each other primarily because of the COOH-terminus of the predicted strUT-1 translation product being extended by 51-amino acid residues compared with shUT. Previously, we noted multiple UT transcripts were present in stingray kidney. We hypothesized that a COOH terminally abbreviated UT isoform, homologous to shUT, would also be present in stingray kidney. Therefore, we used 5'/3' rapid amplification of cDNA ends to identify a 3'UTR-variant (strUT-1a) of the cDNA that encodes (strUT-1), as well as three, 3'UTR-variant cDNAs (strUT-2a,b,c) that encode a second phloretin-sensitive, urea transporter (strUT-2). The 5'UTR and the first 1,132 nucleotides of the predicted coding region of the strUT-2 cDNAs are identical to the strUT-1 cDNAs. The remainder of the coding region contains only five novel nucleotides. The strUT-2 cDNAs putatively encode a 379-amino acid protein, the first 377 amino acids identical to strUT-1 plus 2 additional amino acids. We conclude that 1) a second UT isoform is expressed in the Atlantic stingray and that this isoform is similar in size to the UT previously cloned from the kidney of the dogfish shark, and 2) at least five transcripts encoding the 2 stingray UTs are derived from a single gene product through alternative splicing and polyadenylation.