Bhavna Bhasin

Late antibody-mediated rejection in renal allografts: outcome after conventional and novel therapies.

Background Although several strategies for treating early antibody-mediated rejection (AMR) in kidney transplants have been investigated, evidence on treatment of late AMR manifesting after 6 months is sparse. In this single-center series, we present data on 23 consecutive patients treated for late AMR. Methods Late AMR was diagnosed using Banff 2007 criteria along with presence of donor-specific antibodies (DSA) and acute rise in serum creatinine (SCr). Response to therapy was assessed by improvement in SCr, histologic improvement, and decline in DSA strength. Results Overall, 17% (4/23) had documented nonadherence while 69% (16/23) had physician-recommended reduction in immunosuppression before AMR. Eighteen patients (78%) were treated with plasmapheresis or low-dose IVIg+rituximab; 11 (49%) with refractory AMR also received one to three cycles of bortezomib. While there was an improvement (P=0.02) in mean SCr (2.4 mg/dL) at the end of therapy compared with SCr at the time of diagnosis (2.9 mg/dL), this improvement was not sustained at most recent follow-up. Eleven (48%) patients had no histologic resolution on follow-up biopsy. Lack of histologic response was associated with older patients (odds ratio [OR]=3.17; P=0.04), presence of cytotoxic DSA at time of diagnosis (OR=200; P=0.04), and severe chronic vasculopathy (cv≥2) on index biopsy (OR=50; P=0.06). Conclusions A major setting in which late AMR occurred in our cohort was reduction or change in immunosuppression. Our data demonstrate an inadequate response of late AMR to current and novel (bortezomib) therapies. The benefits of therapy need to be counterweighed with potential adverse effects especially in older patients, large antibody loads, and chronic allograft vasculopathy.

Primary and secondary hyperoxaluria: Understanding the enigma

Hyperoxaluria is characterized by an increased urinary excretion of oxalate. Primary and secondary hyperoxaluria are two distinct clinical expressions of hyperoxaluria. Primary hyperoxaluria is an inherited error of metabolism due to defective enzyme activity. In contrast, secondary hyperoxaluria is caused by increased dietary ingestion of oxalate, precursors of oxalate or alteration in intestinal microflora. The disease spectrum extends from recurrent kidney stones, nephrocalcinosis and urinary tract infections to chronic kidney disease and end stage renal disease. When calcium oxalate burden exceeds the renal excretory ability, calcium oxalate starts to deposit in various organ systems in a process called systemic oxalosis. Increased urinary oxalate levels help to make the diagnosis while plasma oxalate levels are likely to be more accurate when patients develop chronic kidney disease. Definitive diagnosis of primary hyperoxaluria is achieved by genetic studies and if genetic studies prove inconclusive, liver biopsy is undertaken to establish diagnosis. Diagnostic clues pointing towards secondary hyperoxaluria are a supportive dietary history and tests to detect increased intestinal absorption of oxalate. Conservative treatment for both types of hyperoxaluria includes vigorous hydration and crystallization inhibitors to decrease calcium oxalate precipitation. Pyridoxine is also found to be helpful in approximately 30% patients with primary hyperoxaluria type 1. Liver-kidney and isolated kidney transplantation are the treatment of choice in primary hyperoxaluria type 1 and type 2 respectively. Data is scarce on role of transplantation in primary hyperoxaluria type 3 where there are no reports of end stage renal disease so far. There are ongoing investigations into newer modalities of diagnosis and treatment of hyperoxaluria. Clinical differentiation between primary and secondary hyperoxaluria and further between the types of primary hyperoxaluria is very important because of implications in treatment and diagnosis. Hyperoxaluria continues to be a challenging disease and a high index of clinical suspicion is often the first step on the path to accurate diagnosis and management.

HIV Viremia and T-Cell Activation Differentially Affect the Performance of Glomerular Filtration Rate Equations Based on Creatinine and Cystatin C

Background Serum creatinine and cystatin C are used as markers of glomerular filtration rate (GFR). The performance of these GFR markers relative to exogenously measured GFR (mGFR) in HIV-positive individuals is not well established. Methods We assessed the performance of the chronic kidney disease epidemiology collaboration equations based on serum concentrations of creatinine (eGFRcr), cystatin C (eGFRcys) and both biomarkers combined (eGFRcr-cys) in 187 HIV-positive and 98 HIV-negative participants. Measured GFR was calculated by plasma iohexol clearance. Bias and accuracy were defined as the difference between eGFR and mGFR and the percentage of eGFR observations within 30% of mGFR, respectively. Activated CD4 and CD8 T-cells (CD38+ HLA-DR+) were measured by flow cytometry. Results The median mGFR was >100 ml/min/1.73 m2 in both groups. All equations tended to be less accurate in HIV-positive than in HIV-negative subjects, with eGFRcr-cys being the most accurate overall. In the HIV-positive group, eGFRcys was significantly less accurate and more biased than eGFRcr and eGFRcr_cys. Additionally eGFRcys bias and accuracy were strongly associated with use of antiretroviral therapy, HIV RNA suppression, and percentages of activated CD4 or CD8 T-cells. Hepatitis C seropositivity was associated with larger eGFRcys bias in both HIV-positive and HIV-negative groups. In contrast, eGFRcr accuracy and bias were not associated with HIV-related factors, T-cell activation, or hepatitis C. Conclusions The performance of eGFRcys relative to mGFR was strongly correlated with HIV treatment factors and markers of T-cell activation, which may limit its usefulness as a GFR marker in this population.

Hereditary Renal Hypouricemia: A New Role for Allopurinol?

An 18-year-old white, previously healthy male presented tothe Nephrology clinic for evaluation of exercise-inducedacute kidney injury. A month before presentation, heexperienced multiple episodes of vomiting and severe backpain while participating in a 400-meter race. He was takento the Emergency Department and diagnosed with acutekidney injury. He reported a similar episode a few monthsbefore this. There was no history of any infectious illness,myalgias, seizures, hematuria, or illicit drug or alcohol usepreceding this event.Initial laboratory assessment in the Emergency Depart-ment showed: blood urea nitrogen 28 mg/dL, creatinine3.4 mg/dL, and serum uric acid (UA) 1.5 mg/dL; serummyoglobin, creatinine kinase, and aldolase were normal.Urinalysis was unremarkable. Renal function improved withfluid resuscitation, and creatinine returned to baseline,1.0 mg/dL.

A meta-analysis to evaluate the efficacy of statins in children with familial hypercholesterolemia.

This meta-analysis was conducted to evaluate the effect of statins on the lipid profile in pediatric and adolescent patients with familial hypercholesterolemia (FH). Randomized, double-blind, controlled trials comparing statins with placebo were identified through electronic and manual search; percent reductions from baseline were calculated for various lipid parameters. Standardized mean differences (effect size) with 95% confidence interval (CI) were calculated for each study and pooled effect size was calculated. A total of 6 studies were included in the meta-analysis. As compared to placebo, statins caused a significant decrease in total cholesterol (TC) [-3.11% (95% CI -3.46 to -2.99)], low-density lipoprotein (LDL) [-4.01% (95% CI -4.27 to -3.81)], triglyceride (TG) [-1.41 (95% CI -1.66 to -1.26)] and a significant increase in high-density lipoprotein (HDL) [1.12 (95% CI 0.73 1.13)]. In conclusion, statins were shown to have good efficacy for the treatment of FH in children.

Evaluation of Polyuria: The Roles of Solute Loading and Water Diuresis

Polyuria, defined as daily urine output in excess of 3.0 to 3.5L/d, can occur due to solute or water diuresis. Solute-induced polyuria can be seen in hospitalized patients after a high solute load from exogenous protein administration or following relief of urinary obstruction. Similar clinical scenarios are rarely encountered in the outpatient setting. We describe a case of polyuria due to high solute ingestion and excessive water intake leading to a mixed picture of solute and water diuresis. Restriction of the daily solute load and water intake resulted in complete resolution of polyuria. Determination of the daily excreted urinary osmoles may yield important clues to the cause of polyuria and should be included in the routine workup of polyuria.

Online CKD education for medical students, residents, and fellows: training in a new era.

CKD and its complications are associated with substantial morbidity and mortality. Studies have highlighted significant deficiencies in resident knowledge and awareness of CKD and its complications. There is a need to improve CKD education through medical school and residency. There is also a need to provide alternatives to traditional teaching methods to meet the challenges of learning in the context of work-hour restrictions and increasing workload among residents and fellows. Internet-based learning resources offer various educational tools, including websites, kidney blogs, online modules, and smartphone applications, which could potentially and efficiently advance CKD knowledge among medical trainees. In this review, we describe several online resources for CKD education that could be useful for medical students, residents, and fellows. Increased awareness of these tools and their utilization may significantly influence and hopefully improve the recognition and management of patients with CKD. Future studies may help evaluate the effectiveness of these online learning methods and their effect on CKD patient outcomes. In addition, in light of increased concern about nephrology workforce issues, the potential for these online tools to augment interest in nephrology careers should be investigated.

Purulent Pericardial Effusion From Community-Acquired Methicillin-Resistant Staphylococcus aureus

Abstract: Although the incidence of purulent pericarditis has decreased significantly in the modern antibiotic era, a high index of clinical suspicion should be maintained to diagnose this life-threatening illness at an early stage. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a global pathogen and notorious for its ability to cause infection in otherwise healthy individuals. However, it has been associated with purulent pericarditis only in some sporadic case reports. The authors describe a case of purulent pericardial effusion caused by CA-MRSA infection. To the best of our knowledge, this is only the fourth case of CA-MRSA pericarditis to be reported in English literature.

Quiz page January 2014: Cachexia, urinary tract infection, nephromegaly, and kidney failure.

Figure 1. Computed tomography of the abdomen shows bilaterally enlarged kidneys. CLINICAL PRESENTATION A 59-year-old homeless woman with chronic hepatitis C and active alcohol and substance abuse presented with symptoms of nausea and flank pain over the preceding 2 weeks. Physical examination was significant for tachycardia, hypotension, and normal temperature. The patient had cachexia (height, 158 cm; weight, 35 kg; body mass index, 14 kg/m) and bilateral costovertebral angle tenderness. At admission, laboratory test results were notable for serum urea nitrogen level of 264 mg/ dL, serum creatinine level of 13.9 mg/dL, and estimated glomerular filtration rate of 3 mL/min/ 1.73 m by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula. The patient’s most recently known previous serum creatinine level, measured 10 years earlier, was 0.9 mg/dL, corresponding to estimated glomerular filtration rate of 75 mL/min/1.73 m. The patient showed the following values: total carbon dioxide, 12 mEq/L; anion gap, 35 mEq/L; white blood cell count, 54,130 cells/mL; hemoglobin, 10.0 g/dL, which decreased to 6.2 g/dL with hydration; and platelets, 37,000 cells/mL. Urinalysis showed 170 white blood cells per highpower field and urine culture grew pan-sensitive Escherichia coli. Serologic tests for hepatitis B, HIV (human immunodeficiency virus), antinuclear antibodies, antineutrophil cytoplasmic antibodies, complement C3 and C4, and serum and urine protein electrophoresis all produced normal or negative results. Computed tomography (CT) of the abdomen without intravenous contrast (Fig 1) showed bilateral kidney enlargement: the patient’s right kidney was 11 cm and the left kidney was 13.2 cm. There was no significant lymphadenopathy. The patient initiated hemodialysis therapy to manage uremia, and a diagnostic percutaneous kidney biopsy was performed (Figs 2-4).

Vancomycin-Associated Acute Kidney Injury with a Steep Rise in Serum Creatinine

Background: Vancomycin-associated (VA) acute kidney injury (AKI) is being increasingly recognized. A distinct pattern of rapid rise in serum creatinine (sCr) during VA-AKI has occasionally been observed. However, such scenarios remain underreported. Methods: We conducted an online survey at the American Society of Nephrology Communities forum and reviewed publications of VA-AKI via PubMed or Google searching for cases of precipitous AKI (those with rise in sCr ≥1.5 mg/dL/day) attributable to vancomycin. Results: We identified 12 original cases compiled from 6 different hospitals and 4 published cases (n = 16; 38% women, age 43.5 ± 16 years, weight 108 ± 23 kg, body mass index 35 ± 7 kg/m2) of precipitous AKI observed shortly after large cumulative doses of VA (8.8 ± 5 g). The median steepest 24-h rise in sCr was 2.6 mg/dL (range 1.5–3.5 mg/dL) and the slope of the initial 48-h sCr rise was greater than that of a control AKI (non-VA, n = 48) group (2.03 ± 0.1 vs. 0.62 ± 0.0 mg/dL/day; p < 0.0001). The steep rise in sCr in the VA-AKI was not accompanied by anuria. Overt rhabdomyolysis was absent in all cases. Further, in 3 precipitous VA-AKI cases, simultaneous serum cystatin C values did not rise precipitously, suggesting that the reductions in glomerular filtration rate were overestimated by the sCr increase. Conclusions: VA-AKI can manifest with a precipitous rise in sCr shortly after a high cumulative dose of vancomycin. True toxic tubular injury overrepresented by the sCr rise is postulated.