Ganesh Shidham

Staphylococcus Infection-Associated Glomerulonephritis Mimicking IgA Nephropathy

The association of methicillin-resistant Staphylococcus aureus (MRSA) infection with glomerulonephritis (GN) has been well documented in Japan but not in North America. Recently, eight renal biopsies with IgA-predominant or -codominant GN from eight patients with underlying staphylococcal infection, but without endocarditis, were observed at a single institution in a 12-mo period. Renal biopsies were worked up by routinely used methodologies. Eight cases of primary IgA nephropathy were used as controls. Five patients had MRSA infection, one had methicillin-resistant S. epidermidis (MRSE) infection, and two had methicillin-sensitive S. aureus infection. Four patients became infected after surgery; two patients were diabetic and had infected leg ulcers. All patients developed acute renal failure, with active urine sediment and severe proteinuria. Most renal biopsies showed only mild glomerular hypercellularity. Two biopsies had prominent mesangial and intracapillary hypercellularity; one of them (the MRSE-associated case) had large glomerular hyalin thrombi. This patient also had a positive cryoglobulin test. Rare glomerular hyalin thrombi were noted in two other cases. Immunofluorescence showed IgA pre- or codominance in all biopsies. Electron microscopy revealed mesangial deposits in all cases. Five biopsies had rare glomerular capillary deposits as well. In the MRSE-associated GN, large subendothelial electron-dense deposits were present. These cases demonstrate that staphylococcal (especially MRSA) infection-associated GN occurs in the US as well, and a rising incidence is possible. It is important to differentiate a Staphylococcus infection-associated GN from primary IgA nephropathy to avoid erroneous treatment with immunosuppressive medications.

Clinical risk factors associated with bleeding after native kidney biopsy

Purpose:  To determine the effect of various risk factors on postbiopsy bleeding (PBB).

Kidney Complications of Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) exposes a patients kidneys to a unique combination of challenges, including high-dose radiation, anemia, chemotherapeutic agents, graft-versus-host disease, opportunistic infections, attenuated and altered immunologic responses, fluid and electrolyte imbalances, and extensive courses of antimicrobial agents. Since the inception of HSCT in the 1950s, there has been increasing interest in defining, determining, and managing the kidney complications that accompany this procedure. In this article, we review the common causes of acute kidney injury and chronic kidney disease that occur with HSCT, including HSCT-associated thrombotic microangiopathy, a distinct cause of chronic kidney disease with a multifactorial cause previously known as bone marrow transplant nephropathy or radiation nephropathy. Additionally, we review other kidney complications, including calcineurin inhibitor nephrotoxicity and chronic graft-versus-host disease-associated glomerulonephritis, that develop post-HSCT. Critically, due to its grave prognosis, it is important to identify HSCT-associated thrombotic microangiopathy early, as well as distinguish it from the other causes of chronic kidney disease.

Random Spot Urine Protein/Creatinine Ratio Is Unreliable for Estimating 24-Hour Proteinuria in Individual Systemic Lupus Erythematosus Nephritis Patients

Background: Recently the American Rheumatologic Association (ARA) recommended random spot urine protein/creatinine ratio (P/C) to monitor systemic lupus erythematosus (SLE) glomerulonephritis (GN). Shortly afterward, 2 works were published, designated Study 1 and Study 2, which are the only studies to test spot P/C in SLE GN. Here we evaluate Study 1 and Study 2, which came to different conclusions. Methods: Study 1 compared spot P/C to the P/C of intended 24-hour collections >50% complete, which reliably estimates 24-hour proteinuria. Study 2 compared spot P/C to the protein content of intended 24-hour collections >80% complete. To compare studies, Study 2 data were converted to P/C ratios. Results: Study 1 and Study 2 were found to be in agreement. Both showed that spot P/C and 24-hour P/C were highly correlated, but only when compared over the entire P/C range (0–8.0) (r = 0.842). Over the P/C range 0.5–3.0 (the most common P/C range encountered in SLE GN), correlation was present, but concordance was poor, rendering random P/C ratio unreliable. Conclusions: Random spot P/C ratio is unreliable for detecting moderate proteinuria change. For example, random spot P/C would not reliably diagnose British Isles Lupus Assessment Group (BILAG) Category A or B proteinuric flares.

Relationship between albuminuria and total proteinuria in systemic lupus erythematosus nephritis: diagnostic and therapeutic implications.

BACKGROUND AND OBJECTIVES Albuminuria is regarded a sensitive measure of progression of glomerular disease. This study was undertaken in patients who had systemic lupus erythematosus glomerulonephritis (n = 57) and were followed in the Ohio SLE Study to determine whether measuring albuminuria offered clinical advantages over that of total proteinuria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Twenty-four-hour urine collections (n = 127) were obtained at baseline and annually for measurement of microalbumin, total protein, and creatinine. RESULTS There was a strong linear relationship between microalbumin-creatinine and protein-creatinine ratios over the entire range of protein-creatinine ratios; however, in the protein-creatinine ratio range 0.0 to 0.3, as the protein-creatinine ratio increased, the microalbumin-protein ratio increased much more than the protein-creatinine ratio. Also, the greater the protein-creatinine ratio, the greater was the evidence for nonselective proteinuria (protein-creatinine ratio--microalbumin-creatinine ratio). CONCLUSIONS For the diagnosis of proteinuria renal flare, measuring albuminuria offers no advantage over measuring total proteinuria because changes in protein-creatinine and microalbumin-creatinine ratios are highly correlated over the designated ranges for systemic lupus erythematosus glomerulonephritis proteinuric flares. In those with normal-range proteinuria, subsequent changes in microalbumin-protein ratio might be a better forecaster of renal flare than changes in protein-creatinine or microalbumin-creatinine ratio. High protein-creatinine ratios are associated with evidence of nonselective proteinuria, which may increase the nephrotoxicity of proteinuria. Thus, using high-threshold criteria for systemic lupus erythematosus flare (allowing greater proteinuria increase before flare is declared) may expose the kidney to greater nephrotoxicity than using the low-threshold criteria for systemic lupus erythematosus flare.

Spot PC ratio estimates of 24-hour proteinuria are more unreliable in lupus nephritis than in other forms of chronic glomerular disease

Spot urine protein/creatinine ratio (PCR) is often used clinically to estimate 24-hour (24-h) proteinuria. However, urine PCR shows considerable hour to hour variability.1 ,2 In lupus nephritis (LN), spot PCR reveals this variability, while longer timed collections conceal it.3–5 Spot PCR performs well in cohort studies, where its variability is mitigated by averaging the data.6 However, spot PCR variability becomes a liability for individual patient management. This work is the first to compare spot PCR variability in LN and chronic kidney disease (CKD). For LN, we used the published works (N=3, 165 patients) that documented the completeness (creatinine content) of the 24-h urine collections3–5 (LN studies A, B, and C, respectively). For CKD, we used a standard CKD cohort (ramipril efficacy in nephropathy (REIN) Trial, 98 patients), which documented completeness of the collections.6 Almost all spot PCRs were from morning collections. As shown in the calibration …

Diagnostic utility of kidney biopsy in patients with sarcoidosis and acute kidney injury

Background: Sarcoidosis is an idiopathic multisystem disease characterized by noncaseating granulomatous inflammation. Renal biopsy is often performed to evaluate the patient with sarcoidosis and acute kidney injury (AKI). Diagnosis rests on the demonstration of noncaseating granulomas and exclusion of other causes of granulomatous inflammation. This paper reports a patient with pulmonary sarcoidosis and AKI whose renal function improved after prednisone therapy despite the absence of kidney biopsy findings characteristic of sarcoidosis. Case report: A 63-year-old Caucasian male with history of hypertension was treated for pulmonary sarcoidosis with a 6-month course of prednisone. His creatinine was 1.6 mg/dL during the course. Two months after finishing treatment, he presented with creatinine of 4 mg/dL. A kidney biopsy was performed, which showed nonspecific changes without evidence of granuloma or active interstitial inflammation. He was empirically started on prednisone for presumed renal sarcoidosis, even with a nondiagnostic kidney biopsy finding. Within a month of treatment, his serum creatinine improved to 2 mg/dL, though not to baseline. He continues to be stable on low-dose prednisone. With this case as a background, we aimed to determine the incidence of inconclusive kidney biopsies in patients with sarcoidosis presenting with AKI and to identify the various histological findings seen in this group of patients. Methods: In this retrospective study, all patients who had native renal biopsies read at The Ohio State University over the period of 6 years were identified. Those patients with a diagnosis of sarcoidosis, presenting with AKI, were included for further review. Results: Out of 21 kidney biopsies done in patients with sarcoidosis over a period of 6 years, only four (19%) showed granulomatous interstitial nephritis (GIN). An equal number of patients (4 [19%]) had presence of membranous nephropathy. Nephrocalcinosis was seen in three patients (14%). Almost half of the biopsies had findings suggestive of diabetic nephropathy or other nonspecific changes not characteristic of renal sarcoidosis (48%). Conclusion: Renal sarcoidosis can be focal in nature and characteristic lesions can be missed in a small-needle core biopsy. Inconclusive renal biopsies with only nonspecific findings are frequent in patients with sarcoidosis and AKI. The presence of GIN on renal biopsy, although classic, is uncommon. Renal sarcoidosis remains a presumptive clinical diagnosis and empiric treatment with steroids may be initiated in cases with a strong clinical suspicion even in the absence of characteristic renal biopsy findings.

Long-term, sub-clinical cardiac and renal complications in patients with multiple relapses of thrombotic thrombocytopenic purpura.

notes that as a result ‘most recommendations were grade C, level IV’. It should be noted, however, that this system of grading of levels of evidence and the strength of recommendations usually relate to patient treatment that, by definition, is not required in these patients and so there are few or no clinical trials to quote. Most of the recommendations are based on the outcomes of large observational studies and consequently are based on a greater amount of evidence than the clinical trial grading system suggests. There is a need for prospective, randomized clinical studies particularly to establish the role of monitoring in patients with MGUS. Our guidance will be reviewed regularly and will incorporate new evidence as it becomes available but meanwhile, we believe we have interpreted the observational evidence in a responsible and balanced manner, taking into account both individual patient considerations and wider health economic factors.

Bath Salts: A Newly Recognized Cause of Acute Kidney Injury

Bath salts are substance of abuse that are becoming more common and are difficult to recognize due to negative toxicology screening. Acute kidney injury due to bath salt use has not previously been described. We present the case of a previously healthy male who developed acute kidney injury and dialysis dependence after bath salt ingestion and insufflation. This was self-reported with negative toxicology screening. Clinical course was marked by severe hyperthermia, hyperkalemia, rhabdomyolysis, disseminated intravascular coagulation, oliguria, and sepsis. We discuss signs and symptoms, differential diagnoses, potential mechanisms of injury, management, and review of the literature related to bath salt toxicity.

Limited reliability of the spot urine protein/creatinine ration in the longitudinal evaluation of patients with lupus nephritis

Introduction Cross-sectional studies document that the spot protein/creatinine ratio (PCR) is often an inaccurate estimate of proteinuria magnitude compared with the 24-hour PCR, which is the gold standard. However, the extent to which the inaccuracy of the spot PCR varies over time and between individuals has not previously been reported. We address these crucial questions using a unique database, an National Institutes of Health trial in which lupus nephritis (LN) patients (N = 103) provided spot PCR testing each month and 24-hour PCR testing every 3 months for up to 15 months after induction therapy. Methods A gold standard proteinuria trend line was constructed for each patient by joining the points that represented the serial 24-hour PCR values of the patient. The spot PCR values of the patient were then plotted in relationship to the 24-hour PCR trend line. Using our previous work, which estimated the 95% confidence intervals for the 24-hour PCR at specific levels, we determined in each patient whether the spot PCR values were “reliable,” “problematic,” or “unreliable.” The sequential spot PCR of the patients deviated widely and often from the 24-hour PCR trend line, to the extent that, if the spot PCR results were used in real time for clinical decision-making, it was likely management errors would occur. Results Spot PCRs were reliable in 41%, problematic in 24%, and unreliable in 35% of patients. Those with unreliable spot PCRs could not be predicted and were more likely to respond poorly to treatment. Conclusion The spot PCR should not be used for management of LN, and perhaps, other glomerulopathies.