Acute Kidney Injury Associated With Vancomycin When Laxity Leads to Injury and Findings on Kidney Biopsy.

The issue of vancomycin-induced acute kidney injury (AKI) has resurged with the use of intravenous vancomycin as a first-line antibiotic, often for prolonged periods of time for the management of serious methicillin-resistant Staphylococcus aureus infections, and with a higher recommended trough level (15-20 µg/mL). We have observed 3 patients on intravenous vancomycin who developed very high trough levels (>40 µg/mL) and severe (stage 3) AKI. Those 3 patients underwent kidney biopsy for unresolving AKI, which revealed findings compatible with acute tubular necrosis. The first patient initially developed asymptomatic acute interstitial nephritis because of a concomitant antibiotic that caused worsening of kidney function, and the dose of vancomycin was not properly adjusted while staying at the nursing home. The second was an emaciated patient (BMI, 14) whose serum creatinine level was a deceptive marker of kidney function for the proper dosing of vancomycin, resulting in a toxic level. The third patient developed vancomycin-related AKI on an initially high therapeutic level, which then contributed to further rising in vancomycin level and subsequently causing severe AKI. One patient required hemodialysis, but all 3 patients ultimately recovered their kidney function significantly. A regular monitoring (preferably twice weekly) of serum creatinine and vancomycin trough level is advisable to minimize vancomycin-associated AKI, primarily acute tubular necrosis, for patients requiring prolonged administration of vancomycin (>2 weeks) on the currently recommended higher therapeutic trough levels (>15 µg/mL).

Time Is Not Always the Matter: An Instance of Encapsulating Peritoneal Sclerosis Developing in a Patient on Peritoneal Dialysis for a Short Term.

Encapsulating peritoneal sclerosis (EPS) is an infrequent but serious complication that is observed mostly in patients on long-term peritoneal dialysis (PD). However it can occur after short-term PD, in association with "second hit" risk factors such as peritonitis, acute cessation of PD, or kidney transplantation with the use of calcineurin inhibitors.In our case, a young woman with second-hit risk factors presented with clinical and abdominal computed tomography findings consistent with EPS after short-term PD. She was treated conservatively with nutritional support and was discharged in improved and stable clinical status.In general, the diagnosis of EPS requires clinical findings of bowel obstruction combined with typical computed tomography imaging features. However, the clinical manifestations can be very vague, and the diagnosis is often unclear. A recent study categorized EPS into 4 clinical stages, from pre-EPS to chronic ileus, with associated management from conservative treatment to surgical intervention.In association with second-hit risk factors, EPS can occur after short-term PD. Severity is variable, and the outcome is often devastating. Timely recognition and expert management of EPS can change the outcome very favorably.

Diffuse infiltrative lymphocytosis syndrome presenting as reversible acute kidney injury associated with Gram-negative bacterial infection in patients with newly diagnosed HIV infection.

Diffuse infiltrative lymphocytosis syndrome (DILS) is believed to be an immunologic syndrome, most likely in response to human immunodeficiency virus (HIV) antigens, and can be accompanied by decreased kidney function. The spectrum of kidney involvement includes acute or chronic kidney disease, primarily tubular proteinuria; enlarged kidneys on imaging studies; and dense lymphocytic tubulointerstitial infiltrates predominantly composed of CD8(+) T cells on kidney biopsy. We describe 3 newly diagnosed HIV-positive patients of African descent with the histologic and clinical diagnosis of DILS who presented with acute kidney injury associated with Gram-negative bacterial infections. Solely with specific antibiotic therapy without antiviral and/or corticosteroid therapy, all patients recovered from acute kidney injury and had partial to complete resolution of proteinuria and enlarged kidney size. These observations led us to hypothesize that an altered immunologic and/or inflammatory response to the endotoxin derived from Gram-negative bacteria, rather than an immunologic response directed to HIV-related antigens, may be a pathogenetic mechanism for the kidney disease associated with DILS in a subset of HIV-positive patients, especially those of immunogenetically susceptible African descent.

Membranous nephropathy and thrombotic thrombocytopenic purpura treated with rituximab.

A 43-year-old black male was brought to hospital with complaints of confusion and fever. He was noted to have petechial lesions, thrombocytopenia (platelet count 7,200/ml), schistocytes on peripheral smear, and serum creatinine 1.7 mg/dl (150.28 micromol/L). He was diagnosed to have thrombotic thrombocytopenic purpura (TTP) and started on high dose IV steroids and plasmapheresis. Attempts at steroid withdrawal following plasmapheresis were unsuccessful as his platelet count started to decrease. He subsequently was started on rituximab given as 4 weekly infusions. The platelet count normalized after 2 doses of rituximab. A kidney biopsy performed to evaluate proteinuria (10.24 gms/24 hr) revealed membranous nephropathy (MN), with organized obliterative arteriopathy consistent with thrombotic microangiopathy. Upon completion of the treatment, proteinuria decreased to 1.67 gm/24hr. Recent studies indicate that patients with TTP have an inhibitory (auto) antibody to von Willibrand factor cleaving protease (ADAMTS 13). Considerable evidence also exists that idiopathic membranous nephropathy is an autoimmune disease. Rituximab, a monoclonal chimeric antibody directed against CD20 antigen present on B cells, selectively depletes B cells and has been used with success in both diseases. Though evidence for a direct pathogenetic relationship between TTP and MN is lacking, the two entities are more likely related to autoantibodies induced by activation of B cells. For our patient with this rare disease combination rituximab therapy was one treatment solution to two diseases.

Is It Coincidence or Consequence for a Case with Antiphospholipid Antibody Syndrome Overlapping SLE to Develop an Immune Complex Nephropathy Followed by a Nonimmune Complex Podocytopathy?

Antiphospholipid antibody syndrome (APS) may occur in a primary form or in association with SLE and seldom presents with nephrotic syndrome (NS). We present a case with APS who developed recurrent NS 6 years apart. The first episode of NS occurred with biopsy findings consistent with lupus nephritis (LN) class V (membranous) with no clear evidence of SLE, and responded to a remission with steroids and MMF. On the 2nd episode, the biopsy revealed negative immunofluorescent (IF) study for immune complexes and EM findings of complete effacement of foot processes and acellular debris in thickened capillary walls, compatible with healed previous episode of membranous LN and minimal change disease (MCD), a nonimmune complex podocytopathy. The 2nd episode responded to a partial remission, primarily with a short-term steroid therapy, and subsequently developed serologic evidence of SLE. Now there is growing evidence that a subset of SLE patients with NS are found to have MCD, likely due to podocyte injury caused by nonimmune complex pathway, called lupus podocytopathy. In LN, serial kidney biopsies often show transformation from one to another class of immune complex-induced glomerular lesions; however there are rare reports describing transformation of an immune complex to a nonimmune complex LN. Since the pathogenic mechanism of lupus podocytopathy is not delineated, and so far there are no reports on transformation of membranous LN, an immune complex nephropathy, to a nonimmune complex lupus podocytopathy, it still remains as a question whether our case with APS overlapping SLE had a concomitant membranous LN and lupus podocytopathy, or consequential membranous LN and lupus podocytopathy 6 years apart.

Calciphylaxis and subtotal parathyroidectomy: a double-edged sword.

Calciphylaxis, also called calcific uremic arteriolopathy is a dreadful, life-threatening ischemic vasculopathy, primarily involving skin and subcutaneous tissue, mostly on patients with end-stage kidney disease. Calciphylaxis is a well-described, but still a poorly understood disorder of mineral metabolism. Its occurrence is rare, but increasingly reported. We describe a 62-year-old obese lady on hemodialysis for end-stage kidney disease due to type 2 diabetes, who developed two episodes of calciphylactic skin lesions during the 3 years observation. The healing of lesions in the first episode was prompted by a subtotal parathyroidectomy for severe secondary hyperparathyroidism. However, the resumption of oral calcium and vitamin D analog for the parathyroidectomy-related hypocalcemia induced another occurrence of widespread calciphylactic skin lesions in areas of great adiposity. The typical regimen of IV sodium thiosulfate brought a successful outcome to the second episode. Now, growing numbers of successful treatment for calciphylaxis are reported with more specific therapies and a clear understanding of the pathogenetic mechanism is in sight.

Chronic kidney disease staging in nursing home and community older adults: does the choice of cockcroft-gault, modification of diet in renal disease study, or the chronic kidney disease epidemiology collaboration initiative equations matter?

OBJECTIVE: To compare the chronic kidney disease (CKD) stages derived from GFR estimates using 3 different formulae in a sample of older adults from the community and long term care settings. PARTICIPANTS: Data from 1535 older, hospitalized patients (2000-2008) were collected; individuals were hospitalized for acute illness unrelated to renal function. MEASUREMENTS: Patient demographics, pertinent medical history, and routine laboratory test results were collected. Estimate of glomerular filtration rate and creatinine clearance values were determined by the Cockcroft-Gault, Modification of Diet in Renal Disease Study, and Chronic Kidney Disease Epidemiology Collaboration equations. RESULTS: The Cockcroft-Gault equation generated significantly lower mean estimate of glomerular filtration rate values than either Modification of Diet in Renal Disease Study or Chronic Kidney Disease Epidemiology Collaboration equations in the total sample (P < .0005) and in a subset of patients diagnosed as renal insufficiency (P < .00005). Using the 3 formulae produced a significant disconnect in CKD staging resulting in the potential for different recommendations for monitoring and management across formulae (National Kidney Foundation Guidelines) (P < .0005). When stratified by age, the 3 equations produce nearly identical glomerular filtration rate estimates in patients younger than 70 years (P = .989) but significantly different glomerular filtration rate estimates in patients from 70 to 104 years (P < .0005). CONCLUSIONS: The Cockcroft-Gault equation systematically provides lower (more severe) estimates of renal function than the Modification of Diet in Renal Disease Study and Chronic Kidney Disease Epidemiology Collaboration equation in patients older than 70 years. However, significant differences in CKD staging derived from estimate of glomerular filtration rate or creatinine clearance were not observed in adults from 59 to 69 years of age. These findings do not validate one formula over the others, but demonstrate that disparities exist; it may be prudent to use the same formula over time in a given patient to monitor changes in renal function.