The spectrum of sickle hemoglobin-related nephropathy: from sickle cell disease to sickle trait

Renal dysfunction is among the most common complication of sickle cell disease (SCD), from hyposthenuria in children to progression to overt chronic kidney disease (CKD) in young adults. Emerging evidence now suggests that sickle hemoglobin-related nephropathy extends to individuals with sickle cell trait (SCT)

Editorial: Pathogenesis and management of glomerular diseases

Glomerular diseases are considered to be the result of inherited or acquired disorders and may manifest in a variety of clinical syndromes, including numerous pictures in terms of severity. A significant number of patients have no symptoms while others discover urinary abnormalities in routine screenings or they may experience low grade symptoms, such as macroscopic hematuria and edema in the lower extremities. Occasional patients present with rapidly progressive glomerulonephritis, a serious condition which may end up in advanced or end-stage kidney disease if remain untreated. Renal histopathology evaluation in combination with the characteristics of the clinical syndrome remains the cornerstone for accurate diagnosis and evidence-based treatment. During the past decade substantial progress has been made in this field, especially regarding the etiology and pathogenesis of these diseases. Recent knowledge has been added, including molecular mechanisms, genetic associations and immunologically-mediated forms of glomerulonephritis, underlining the autoimmune basis associated with genetic risk factors and environmental stimulus leading to immune-mediated injury of the glomeruli

The glomerulopathy of sickle cell disease

Sickle cell disease (SCD) produces many structural and functional abnormalities in the kidney, including glomerular abnormalities. Albuminuria is the most common manifestation of glomerular damage, with a prevalence between 26 and 68% in adult patients. The pathophysiology of albuminuria in SCD is likely multifactorial, with contributions from hyperfiltration, glomerular hypertension, ischemia-reperfusion injury, oxidative stress, decreased nitric oxide (NO) bioavailability, and endothelial dysfunction. Although its natural history in SCD remains inadequately defined, albuminuria is associated with increased echocardiography-derived tricuspid regurgitant jet velocity, systemic blood pressure, and hypertension, as well as history of stroke, suggesting a shared vasculopathic pathophysiology. While most patients with albuminuria are treated with angiotensin converting enzyme inhibitors/angiotensin receptor blockers, there are no published long-term data on the efficacy of these agents. With the improved patient survival following kidney transplantation, SCD patients with end-stage renal disease should be considered for this treatment modality. Given the high prevalence of albuminuria and its association with multiple SCD-related clinical complications, additional studies are needed to answer several clinically important questions in a bid to adequately elucidate its pathophysiology, natural history, and treatment

Polyomavirus Nephropathy: Quantitative Urinary Polyomavirus-Haufen Testing Accurately Predicts the Degree of Intrarenal Viral Disease

BackgroundA qualitative highly predictive urinary test for polyomavirus nephropathy (PVN) is the PV-Haufen test. This article evaluates whether a quantitative PV-Haufen analysis, that is, the number of PV-Haufen shed per milliliter urine, predicts PVN disease grades and the severity of intrarenal PV replication.MethodsPolyomavirus-Haufen were counted in 40 urine samples from patients with biopsy-proven definitive PVN. The number of PV-Haufen was correlated with both histologic PVN disease grades 1 to 3 and the number of SV40-T–expressing cells as indicators of intrarenal PV replication in corresponding renal allograft biopsies (manual counts and automated morphometry). Findings from quantitative PV-Haufen analyses were compared to conventional laboratory test results, that is, BK viremia (quantitative polymerase chain reaction [PCR]) and BK viruria (quantitative PCR and decoy cell counts).ResultsPolyomavirus-Haufen counts showed excellent correlation (α0.77–0.86) with the severity of intrarenal PV replication and disease grades. In particular, low PV-Haufen numbers strongly correlated with early PVN grade 1 and minimal intrarenal expression of SV40-T antigen (P < 0.001). In comparison, BK viremia and viruria levels by PCR showed only modest correlations with histologic SV40-T expression (α0.40–0.49) and no significant correlation with disease grades or minimal intrarenal PV replication. No correlations were seen with urinary decoy cell counts. In contrast to conventional quantitative PCR assays or decoy cell counts, quantitative urinary PV-Haufen testing accurately reflects the severity of PV replication, tissue injury, and PVN disease grades.ConclusionsQuantitative PV-Haufen testing is a novel noninvasive approach to patient management for the diagnosis and prediction of PVN disease grades and monitoring of disease course during therapy.Quantitative testing of polyoma virus within shed renal tubule cells in the urine is superior to conventional BKV urinary or blood quantitation to define both the presence and degree of polyoma nephropathy. Supplemental digital content is available in the text

Diagnostic Significance of Peritubular Capillary Basement Membrane Multilaminations in Kidney Allografts: Old Concepts Revisited

Injury to peritubular capillaries and capillary basement membrane multilamination (PTCL) is a hallmark of antibody-mediated chronic renal allograft rejection. However, the predictive diagnostic value of PTCL is incompletely studied

Hydroxyurea is associated with lower prevalence of albuminuria in adults with sickle cell disease

Albuminuria is an early manifestation of sickle cell nephropathy. Prior small case series suggests benefit of hydroxyurea in reducing albuminuria, with a similar trend noted in pediatric studies. We aimed to comprehensively evaluate hydroxyurea use and prevalence of albuminuria in adult sickle cell patients

Albuminuria Is Associated with Endothelial Dysfunction and Elevated Plasma Endothelin-1 in Sickle Cell Anemia

The pathogenesis of albuminuria in SCD remains incompletely understood. We evaluated the association of albuminuria with measures of endothelial function, and explored associations of both albuminuria and measures of endothelial function with selected biological variables (vascular endothelial growth factor [VEGF], endothelin-1 [ET-1], soluble fms-like tyrosine kinase-1 [sFLT-1], soluble vascular cell adhesion molecule-1 [soluble VCAM-1] and plasma hemoglobin)

Sugar-sweetened soda consumption, hyperuricemia, and kidney disease

The metabolism of high-fructose corn syrup used to sweeten soda drinks may lead to elevations in uric acid levels. Here we determined whether soda drinking is associated with hyperuricemia and, as a potential consequence, reduced kidney function. At baseline, 15,745 patients in the Atherosclerosis Risk in Communities Study completed a dietary questionnaire and had measurements of their serum creatinine and uric acid. After 3 and 9 years of follow-up, multivariate odds ratios from logistic regressions for binary outcome of hyperuricemia and chronic kidney disease (eGFR less than 60 ml/min per 1.73 m2) were evaluated. Compared to participants who drank less, consumption of over one soda per day was associated with increased odds of prevalent hyperuricemia and chronic kidney disease. The odds ratio for chronic kidney disease significantly increased to 2.59 among participants who drank more than one soda per day and had a serum uric acid level over 9.0 mg/dl. In longitudinal analyses, however, drinking more than one soda per day was not associated with hyperuricemia or chronic kidney disease. Neither preexistent hyperuricemia nor development of hyperuricemia modified the lack of association between soda drinking and incident chronic kidney disease. Thus our study shows that high consumption of sugar-sweetened soda was associated with prevalent but not incident hyperuricemia and chronic kidney disease

Sickle Cell Trait and Incident Ischemic Stroke in the Atherosclerosis Risk in Communities Study

Numerous case reports describe stroke in individuals with sickle cell trait (SCT) in the absence of traditional risk factors for cerebrovascular disease. To date, no prospective epidemiological studies have investigated this association