Atypical hemolytic uremic syndrome (aHUS) is a disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. The histopathologic lesions of aHUS include thrombotic microangiopathy involving the glomerular capillaries and thrombosis involving arterioles or interlobar arteries. Extra-renal manifestations occur in up to 20% of patients. The majority of aHUS is caused by complement system defects impairing ordinary regulatory mechanisms. Activating events therefore lead to unbridled, ongoing complement activity producing widespread endothelial injury. Pathologic mutations include those resulting in loss-of-function in a complement regulatory gene (CFH, CFI, CD46 or THBD) or gain-of-function in an effector gene (CFB or C3). Treatment with the late complement inhibitor, eculizumab - a monoclonal antibody directed against C5 - is effective.

Among the spectrum of disease manifestations associated with systemic lupus erythematosus, lupus nephritis is particularly concerning due to the potential for renal failure. This autoimmune attack may not, however, be limited to the kidney and is increasingly being recognized as a trigger for atypical Hemolytic Uremic Syndrome (aHUS). Atypical HUS falls under the spectrum of the thrombotic microangiopathies (TMAs) - a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ damage. Although plasma exchange is considered first-line therapy for thrombotic thrombocytopenic purpura - a TMA classically associated with autoimmune depletion of ADAMTS-13 - aHUS demonstrates less reliable responsiveness to this modality. Instead, use of the late complement inhibitor Eculizumab has emerged as an effective modality for the management of such patients. Diagnosis of aHUS, however, is largely clinically based, relying heavily upon a multidisciplinary approach. Herein we present the case of a patient with atypical HUS successfully treated with Eculizumab in the setting of Class IV-G (A) lupus nephritis and hypocomplementemia.

Physician caseload may be a predictor of patient outcomes associated with various medical conditions and procedures, but the association between patient-physician ratio and mortality among patients undergoing hemodialysis has not been determined. We examined whether a higher patient-nephrologist ratio affects patient mortality risk using de-identified data from DaVita dialysis clinics and the U.S. Renal Data System. A total of 41 nephrologists with a caseload of 50-200 hemodialysis patients from an urban California region were retrospectively ranked according to their hemodialysis patient mortality rate during a 6-year period between 2001 and 2007. We calculated all-cause mortality hazard ratios for each nephrologist and compared patient- and provider-level characteristics between the 10 nephrologists with the highest patient mortality rates and the 10 nephrologists with the lowest patient mortality rates. Nephrologists with the lowest patient mortality rates had significantly lower patient caseloads than nephrologists with the highest mortality rates (median [interquartile range], 65 [55-76] versus 103 [78-144] patients per nephrologist, respectively; P<0.001). Additionally, patients treated by nephrologists with the lowest patient mortality rates received higher dialysis doses, had longer sessions, and received more kidney transplants. In demographic characteristic-adjusted analyses, each 50-patient increase in caseload was associated with a 2% increase in patient mortality risk (hazard ratio, 1.02; 95% confidence interval, 1.00 to 1.04; P<0.001). Hence, these results suggest that nephrologist caseload influences hemodialysis patient outcomes, and future research should focus on identifying the factors underlying this association.

The incidence of early stage renal cell carcinoma (RCC) is increasing and observational studies have shown equivalent oncological outcomes of partial versus radical nephrectomy for stage I tumours. Population studies suggest that compared with radical nephrectomy, partial nephrectomy is associated with decreased mortality and a lower rate of postoperative decline in kidney function. However, rates of chronic kidney disease (CKD) in patients who have undergone nephrectomy might be higher than in the general population. The risks of new-onset or accelerated CKD and worsened survival after nephrectomy might be linked, as kidney insufficiency is a risk factor for cardiovascular disease and mortality. Nephron-sparing approaches have, therefore, been proposed as the standard of care for patients with type 1a tumours and as a viable option for those with type 1b tumours. However, prospective data on the incidence of de novo and accelerated CKD after cancer nephrectomy is lacking, and the only randomized trial to date was closed prematurely. Intrinsic abnormalities in non-neoplastic kidney parenchyma and comorbid conditions (including diabetes mellitus and hypertension) might increase the risks of CKD and RCC. More research is needed to better understand the risk of CKD post-nephrectomy, to develop and validate predictive scores for risk-stratification, and to optimize patient management.

Introduction

Uremia results in a characteristic breath odor (uremic fetor) which is largely due to its high ammonia content. Earlier studies have shown a strong correlation between breath ammonia and blood urea levels and a 10-fold reduction in breath ammonia after hemodialysis in patients with chronic kidney disease. Potential sources of breath ammonia include: (i) local ammonia production from hydrolysis of urea in the oropharyngeal and respiratory tracts by bacterial flora, and (ii) release of circulating blood ammonia by the lungs. While the effects of uremia and hemodialysis on breath ammonia are well known their effects on blood ammonia are unknown and were explored here.

Methods

Blood samples were obtained from 23 hemodialysis patients (immediately before and after dialysis), 14 peritoneal dialysis patients, and 10 healthy controls. Blood levels of ammonia, creatinine, urea, and electrolytes were measured.

Findings

No significant difference was found in baseline blood ammonia between hemodialysis, peritoneal dialysis and control groups. Hemodialysis procedure led to a significant reduction in urea concentration (P < 0.001) which was paradoxically accompanied by a modest but significant (P < 0.05) rise in blood ammonia level in 10 of the 23 patients studied. Change in blood ammonia pre- and post-hemodialysis correlated with change in serum bicarbonate levels (r = 0.61, P < 0.01). On subgroup analysis of patients who had a rise in blood ammonia levels after dialysis, there was a strong correlation with drop in mean arterial pressure (r = 0.88, P < 0.01). The nadir intradialytic systolic blood pressure trended lower in the hemodialysis patients who had a rise in blood ammonia compared to the patients who manifested a fall in blood ammonia (124 ± 8 vs. 136 ± 6 mmHg respectively, P = 0.27).

Discussion

Fall in blood urea following hemodialysis in ESRD patients was paradoxically accompanied by a modest rise in blood ammonia levels in 43% of the patients studied, contrasting prior reported effects of hemodialysis on breath ammonia. In this subgroup of patients, changes in blood ammonia during hemodialysis correlated with rise in blood bicarbonate and fall in mean arterial blood pressure.

Background

Sodium disarrays are common in peritoneal dialysis (PD) patients, and may be associated with adverse outcomes in this population. However, few studies of limited sample size have examined the association of serum sodium with mortality in PD patients, with inconsistent results. We hypothesized that both hypo- and hypernatremia are associated with higher death risk in a nationally representative cohort of US PD patients.

Methods

We sought to examine the association of serum sodium over time and mortality among 4687 adult incident PD patients from a large US dialysis organization who underwent one or more serum sodium measurements within the first 3 months of dialysis over January 2007 to December 2011. We examined the association of time-dependent and baseline sodium with all-cause mortality as a proxy of short- and long-term sodium-mortality associations, respectively. Hazard ratios were estimated using Cox models with three adjustment levels: minimally adjusted, case-mix adjusted, and case-mix + laboratory adjusted.

Results

In time-dependent analyses, sodium levels <140 mEq/L were associated with incrementally higher death risk in case-mix models (ref: 140 to <142 mEq/L); following laboratory covariate adjustment, associations between lower sodium and higher mortality remained significant for levels <136 mEq/L. In analyses using baseline values, sodium levels <140 mEq/L were associated with higher mortality risk across all models (ref: 140 to <142 mEq/L).

Conclusions

In PD patients, lower time-dependent and baseline sodium levels were independently associated with higher death risk. Further studies are needed to determine whether correction of dysnatremia improves longevity in this population.