Long-term sequelae of severe acute kidney injury in the critically Ill patient without comorbidity: A retrospective cohort study

Background and Objectives: Acute kidney injury (AKI) necessitating renal replacement therapy (RRT) is associated with high mortality and increased risk for end stage renal disease. However, it is unknown if this applies to patients with a preliminary unremarkable medical history. The purpose of this study was to describe overall and renal survival in critically ill patients with AKI necessitating RRT stratified by the presence of comorbidity. Design, Setting, Participants, and Measurements: A retrospective cohort study was performed, between 1994 and 2010, including all adult critically ill patients with AKI necessitating RRT, stratified by the presence of comorbidity. Logistic regression, survival curve and cox proportional hazards analyses were used to evaluate overall and renal survival. Standardized mortality rate (SMR) analysis was performed to compare long-term survival to the predicted survival in the Dutch population. Results: Of the 1067 patients included only 96(9.0%) had no comorbidity. Hospital mortality was 56.6% versus 43.8% in patients with and without comorbidity, respectively. In those who survived hospitalization 10-year survival was 45.0% and 86.0%, respectively. Adjusted for age, sex and year of treatment, absence of comorbidity was not associated with hospital mortality (OR=0.74, 95%-CI=0.47-1.15), while absence of comorbidity was associated with better long-term survival (adjusted HR=0.28, 95%-CI = 0.14-0.58). Compared to the Dutch population, patients without comorbidity had a similar mortality risk (SMR=1.6, 95%-CI=0.7-3.2), while this was increased in patients with comorbidity (SMR=4.8, 95%-CI=4.1-5.5). Regarding chronic dialysis dependency, 10-year renal survival rates were 76.0% and 92.9% in patients with and without comorbidity, respectively. Absence of comorbidity was associated with better renal survival (adjusted HR=0.24, 95%-CI=0.07-0.76). Conclusions: While hospital mortality remains excessively high, the absence of comorbidity in critically ill patients with RRT-requiring AKI is associated with a relative good long-term prognosis in those who survive hospitalization

Diagnostic value of urinary dysmorphic erythrocytes in clinical practice

Background: In clinical practice, discriminating between glomerular and nonglomerular causes of hematuria is often difficult. Dysmorphic red blood cells (dRBC) in the urinary sediment are claimed to be effective, but the cutoff points in the literature vary. This follow-up study aimed to determine the diagnostic value of dRBC. Methods: We investigated 134 hematuria patients in the departments of nephrology and urology. To diagnose the origin of hematuria, urological and/or nephrological examination was performed and the %dRBC identified by microscopy. Follow-up was performed after 3.5 years. Results: The cause of hematuria was proven in 68 patients (35% glomerular; 65% nonglomerular). Patients with glomerular disease had significantly more albuminuria and dRBC than patients with nonglomerular disease, but the %dRBC ranged from 1 to 50% and no optimal cutoff could be identified. Logistic regression analysis showed that %dRBC had a predicted probability to diagnose glomerular disease of 77.9% (area under the curve, AUC, 0.85). When %dRBC was combined with other risk factors such as serum creatinine, sex, age, dipstick erythrocyte or proteinuria score and number of casts, the predictive probability increased to 90.6% (AUC 0.97). Follow-up of the included patients showed no benefit of dRBC to identify patients at risk for glomerular disease. Conclusions: The diagnostic value of routinely collected urinary dRBC to diagnose glomerular disease in patients presenting with hematuria is modest. However, including dRBC with other variables, such as age and erythrocyte score on dipstick testing may increase the sensitivity, but needs to be confirmed in another, preferably larger, population. Copyrigh

Potential Deleterious Effects of Vasopressin in Chronic Kidney Disease and Particularly Autosomal Dominant Polycystic Kidney Disease

The antidiuretic hormone vasopressin is crucial for regulating free water clearance in normal physiology. However, it has also been hypothesized that vasopressin has deleterious effects on the kidney. Vasopressin is elevated in animals and patients with chronic kidney disease. Suppression of vasopressin activity reduces proteinuria, renal hypertrophy, glomerulosclerosis and tubulointerstitial fibrosis in animal models. The potential detrimental influence of vasopressin is probably mediated by its effects on mesangial cell proliferation, renin secretion, renal hemodynamics, and blood pressure. In this review, we discuss the increasing body of evidence pointing towards the contribution of vasopressin to chronic kidney disease progression in general and to autosomal dominant polycystic kidney disease in particular. These data allude to the possibility that interventions directed at lowering vasopressin activity, for example by the administration of vasopressin receptor antagonists or by drinking more water, may be beneficial in chronic kidney disease. Copyright (C) 2011 S. Karger AG, Base

Serum bicarbonate is associated with kidney outcomes in autosomal dominant polycystic kidney disease

BACKGROUND: Metabolic acidosis accelerates progression of chronic kidney disease, but whether this is also true for autosomal dominant polycystic kidney disease (ADPKD) is unknown. METHODS: Patients with ADPKD from the DIPAK (Developing Interventions to halt Progression of ADPKD) trial were included [n = 296, estimated glomerular filtration rate (eGFR) 50 ± 11 mL/min/1.73 m(2), 2.5 years follow-up]. Outcomes were worsening kidney function (30% decrease in eGFR or kidney failure), annual eGFR change and height-adjusted total kidney and liver volumes (htTKV and htTLV). Cox and linear regressions were adjusted for prognostic markers for ADPKD [Mayo image class and predicting renal outcomes in ADPKD (PROPKD) scores] and acid–base parameters (urinary ammonium excretion). RESULTS: Patients in the lowest tertile of baseline serum bicarbonate (23.1 ± 1.6 mmol/L) had a significantly greater risk of worsening kidney function [hazard ratio = 2.95, 95% confidence interval (CI) 1.21–7.19] compared with patients in the highest tertile (serum bicarbonate 29.0 ± 1.3 mmol/L). Each mmol/L decrease in serum bicarbonate increased the risk of worsening kidney function by 21% in the fully adjusted model (hazard ratio = 1.21, 95% CI 1.06–1.37). Each mmol/L decrease of serum bicarbonate was also associated with further eGFR decline (−0.12 mL/min/1.73 m(2)/year, 95% CI −0.20 to −0.03). Serum bicarbonate was not associated with changes in htTKV or htTLV growth. CONCLUSIONS: In patients with ADPKD, a lower serum bicarbonate within the normal range predicts worse kidney outcomes independent of established prognostic factors for ADPKD and independent of urine ammonium excretion. Serum bicarbonate may add to prognostic models and should be explored as a treatment target in ADPKD

Urinary markers of intrarenal renin-angiotensin system activity in vivo

Recent interest focuses on urinary renin and angiotensinogen as markers of renal renin-angiotensin system activity. Before concluding that these components are independent markers, we need to exclude that their presence in urine, like that of albumin (a protein of comparable size), is due to (disturbed) glomerular filtration. This review critically discusses their filtration, reabsorption and local release. Given the close correlation between urinary angiotensinogen and albumin in human studies, it concludes that, in humans, urinary angiotensinogen is a filtration barrier damage marker with the same predictive power as urinary albumin. In contrast, in animals, tubular angiotensinogen release may occur, although tubulus-specific knockout studies do not support a functional role for such angiotensinogen. Urinary renin levels, relative to albumin, are >200-fold higher and unrelated to albumin. This may reflect release of renin from the urinary tract, but could also be attributed to activation of filtered, plasma-derived prorenin and/or incomplete tubular reabsorption

Preload dependence of new Doppler techniques limits their utility for left ventricular diastolic function assessment in hemodialysis patients

Left ventricular (LV) hypertrophy leads to diastolic dysfunction. Standard Doppler transmitral and pulmonary vein (PV) flow velocity measurements are preload dependent. New techniques such as mitral annulus velocity by Doppler tissue imaging (DTI) and LV inflow propagation velocity measured from color M-mode have been proposed as relatively preload-independent measurements of diastolic function. These parameters were studied before and after hemodialysis (HD) with ultrafiltration to test their potential advantage for LV diastolic function assessment in HD patients. Ten patients (seven with LV hypertrophy) underwent Doppler echocardiography 1 h before, 1 h after, and 1 d after HD. Early (E) and atrial (A) peak transmitral flow velocities, peak PV systolic (s) and diastolic (d) flow velocities, peak e and a mitral annulus velocities in DTI, and early diastolic LV flow propagation velocity (V(p)) were measured. In all patients, the E/A ratio after HD (0.54; 0.37 to 1.02) was lower (P < 0.01) than before HD (0.77; 0.60 to 1.34). E decreased (P < 0.01), whereas A did not. PV s/d after HD (2.15; 1.08 to 3.90) was higher (P < 0.01) than before HD (1.80; 1.25 to 2.68). Tissue e/a after HD (0.40; 0.26 to 0.96) was lower (P < 0.01) than before HD (0.56; 0.40 to 1.05). Tissue e decreased (P < 0.02), whereas a did not. V(p) after HD (30 cm/s; 16 to 47 cm/s) was lower (P < 0.01) than before HD (45 cm/s; 32 to 60 cm/s). Twenty-four hours after the initial measurements values for E/A (0.59; 0.37 to 1.23), PV s/d (1.85; 1.07 to 3.38), e/a (0.41; 0.27 to 1.06), and V(p) (28 cm/s; 23 to 33 cm/s) were similar as those taken 1 h after HD. It is concluded that, even when using the newer Doppler techniques DTI and color M-mode, pseudonormalization, which was due to volume overload before HD, resulted in underestimation of the degree of diastolic dysfunction. Therefore, the advantage of these techniques over conventional parameters for the assessment of LV diastolic function in HD patients is limited. Assessment of LV diastolic function should not be performed shortly before HD, and its time relation to HD is essential

Single-shot, high-dose rabbit ATG for rejection prophylaxis after kidney transplantation

We studied the effects of a single intravenous injection of rabbit ATG (RIVM, Bilthoven, The Netherlands) in a dose of 8 mg/kg body weight administered 6 h after kidney transplantation on graft survival, rejection incidence, T-cell subsets, and cost-effectiveness. A total of 58 (37 male/21 female) consecutive renal allograft recipients were entered in this trial. Treatment results were compared with 56 patients treated with intravenous cyclosporin (CyA). In all patients concomitant medication consisted of steroids and azathioprine, followed by oral CyA. Following rabbit ATG, T cells (WT31) quickly disappeared from the peripheral blood and a return to greater than 100/mm3 was observed at a median of 7 (range 3–21) days. Graft survival was the same in both groups, as was the incidence of primary nonfunction. The rate of acute rejection was significantly lower in the rabbit ATG-treated patients (12 % vs 50%). We conclude that a single shot of rabbit ATG is an attractive, easy, and cost-effective induction scheme with a low incidence of delayed graft function and acute rejection episodes. A relatively high incidence of vascular thrombosis of the graft, however, warrants further study before this treatment regimen can be generally applied

A series of patients with minimal change nephropathy treated with rituximab during adolescence and adulthood

__Background:__ The treatment of immune suppression dependent minimal change nephropathy (MCN) can be challenging and frequently leads to serious complications. In paediatric patients, successful treatment with rituximab is described in steroid-dependent MCN. There is limited information about the potential efficacy of rituximab for the treatment of MCN in adults and adolescence. We describe our experience with rituximab in adolescent and adult patients with immune suppression dependent MCN. __Results:__ Ten adolescents and adults with immune suppression dependent MCN and therapy related complications were treated with rituximab. At a mean age of 26 years, about 10.5 years after first presentation, they received two doses of rituximab (375 mg/m2). Maintenance immunosuppressive medication was stopped. After a mean follow-up of 43 months, three patients had four relapses. Three relapses were successfully retreated with rituximab again, after induction therapy with 60 mg prednisone per day. Rituximab was well tolerated and no infectious complications were recorded. __Conclusion:__ Treatment with rituximab induces a long-term remission of immune suppression dependent MCN in adolescents and adults. A timely treatment with rituximab could be considered to limit side effects of immunosuppressive medication