The use of eculizumab in gemcitabine induced thrombotic microangiopathy.

BACKGROUND: Thrombotic microangiopathy (TMA) secondary to gemcitabine therapy (GiTMA) is a very rare pathology that carries a poor prognosis, with nearly half of the cases progressing to end stage renal disease. GiTMA is most commonly associated with adenocarcinomas, most notably pancreatic cancers. The mainstay of management is withdrawal of the offending drug and supportive care. Plasmapheresis has a limited role and hemodialysis may help in the management of fluid overload secondary to renal failure. Furthermore, a C5 inhibitor, eculizumab, has been successfully used in the treatment of GiTMA. CASE PRESENTATION: A 64-year-old Caucasian female with history of pancreatic adenocarcinoma on gemcitabine chemotherapy presented with signs and symptoms of fluid overload and was found to have abnormal kidney function. Her BP was 195/110 mmHg, serum creatinine 4.48 mg/dl, hemoglobin 8.2 g/dl, platelets 53 × 103/cmm, lactate dehydrogenase 540 IU/L, and was found to have schistocytes on blood film. A diagnosis of TMA secondary to gemcitabine therapy was suspected. Hemodialysis for volume overload and daily plasmapheresis were initiated. After six days of plasmapheresis, renal function did not improve. Further work up revealed ADAMTS 13 activity >15%, low C3, and stool culture and Shiga-toxin PCR were negative. Renal biopsy was consistent with TMA. Gemcitabine was discontinued, but renal function failed to improve and eculizumab therapy was considered due to suspicion of aHUS. Serum creatinine >2.26 mg/dl and a platelet count of >/= 30 × 109/L is highly suggestive of aHUS, while TTP is more likely when creatinine is <2.26 mg/dl and platelet count of <30 × 109/L. She received intravenous eculizumab for eight months, which resulted in significant improvement of renal function. Other markers of hemolysis, namely LDH and bilirubin, also rapidly improved following eculizumab therapy. Plasmapheresis and hemodialysis were discontinued after two and eight weeks of initiation respectively. CONCLUSION: Chemotherapy induced TMA is very rare and requires a high index of clinical suspicion for timely diagnosis. Discontinuation of the offending drug and supportive care is the main stay of treatment; however, eculizumab has been shown to be beneficial in GiTMA. Further research is required to validate this approach.

Infection associated acute interstitial nephritis; a case report.

BACKGROUND: Acute interstitial nephritis (AIN) is a clinico-pathological syndrome associated with a variety of infections, drugs, and sometimes with unknown causes. It is a common cause of acute kidney injury (AKI) and subsequent renal impairment, which often times is under-diagnosed. Infection-associated AIN occurs as a consequence of many systemic bacterial, viral, and parasitic infec-tions; however, its incidence has decreased significantly after the advent of antimicrobials. Infection-associated AIN presents with both oliguric or non-oliguric renal insufficiency, without the classical clinical triad of AIN (fever, rash, and arthralgia). In this scenario the renal function is usually reversible after the infection is treated. In most cases, patients with acute renal failure present with extra-renal manifestations typically detected in underlying infections. Renal biopsy serves as the most definitive test for both the diagnosis and prognosis of AIN. CASE PRESENTATION: In this paper, we will address one such case of biopsy-proven AIN. In this case, the patient presented with severe AKI induced by anaerobic streptococcus, leading to a periodontal abscess, which was successfully treated with corticosteroids and requiring renal replacement therapy (RRT). CONCLUSIONS: AIN should be considered in the differential for unexplained AKI. Initial management should include conservative therapy by withdrawing any suspected causative agent. Renal biopsy is needed for confirmation in cases where kidney function fails to improve within 5-7 days on conservative therapy. Risk of immunosuppression is very important to consider when giving steroids in patients with infection induced AIN, and steroids may have to be delayed until the active infection is completely controlled.

Waldenström's macroglobulinemia and nephrotic syndrome with membranous nephropathy.

Renal complications of Waldenström's macroglobulinemia (WM) are rarely observed. Nephrotic syndrome in association with WM has most often been secondary to amyloidosis. This article reports a case of WM with nephrotic syndrome as a result of membranous nephropathy with immunoglobulin M (IgM) deposition. A 44-year-old male diagnosed with WM 4 years previously, presented with heavy proteinuria (7.8 g/24 h). Kidney biopsy revealed expanded mesangium, thickened capillary loops and epimembranous spikes, with no significant interstitial inflammation or thickened tubular basement membranes. Immunofluorescence examination demonstrated strong granular staining of IgM and λ chains, with weaker C3 and C1q staining. Electron microscopy showed many subepithelial dense deposits, and fewer large subendothelial dense deposits. Treatment was directed at the patient's WM with maintenance rituximab and fludarabine. Subsequently, decreases were seen in both the patient's serum IgM and serum viscosity. With therapy for WM and the addition of an angiotensin receptor blocker, the patient's proteinuria also improved, from 7.8 g to 4.8 g/24 h. The patient continued to follow up with his hematologist and in 2009 creatinine was 1 mg/dl (76.26 ?mol/l), with a 24 h urine protein excretion of 0.159 g.

Screening for nephropathy and antiangiotensin use among diabetic patients in an academic community medical center.

The American Diabetes Association recommends routine screening for albuminuria to detect early nephropathy in all patients with diabetes mellitus. If nephropathy is identified, treatment with an antiangiotensin agent decreases progression and improves renal outcomes. Concordance with guidelines for nephropathy screening and antiangiotensin therapy among diabetic patients in a primary care setting of an academic community medical center was evaluated. Medical charts of adult patients with diabetes mellitus from February 2000 through January 2003 were retrospectively reviewed. In part 1 of the study, whether patients were screened for nephropathy at least once was recorded. In part 2 of the study, antiangiotensin prescribing was assessed in all patients and in subgroups stratified by screening. In both parts of the study, patient characteristics and comorbidities were assessed using multivariate analysis to determine their impact on the odds that a patient was screened and that antiangiotensin therapy was prescribed. Among the 329 patients included, 182 patients (55.3%) were screened for nephropathy. Patients who were screened were younger (OR=0.83 for 10-year increase, 95% CI: 0.69-0.99), less likely to have congestive heart failure (OR=0.42, 95% CI: 0.20-0.90), and more likely to be cared for by a resident physician directly supervised by an attending physician (OR=3.03; 95% CI: 1.82-5.03). A total of 215 patients (65.3%) were prescribed antiangiotensin therapy. Hypertension was a predictor of antiangiotensin therapy among all patients who were screened (OR=10.34, 95% CI: 4.45-24.01), those who were screened and negative (OR=15.46, 95% CI: 5.56-42.98), and those who were not screened (OR=10.79, 95% CI: 4.39-26.52). Among patients screened for nephropathy, coronary artery disease (OR=3.01, 95% CI: 1.05-8.63), and the presence of proteinuria (OR=4.26, 95% CI: 1.61-11.24) were predictors of antiangiotensin use. This study found that the likelihood of screening for nephropathy among diabetic patients was inversely associated with a diagnosis of congestive heart failure and increasing age. Conversely, care by a resident physician directly supervised by an attending physician increased the odds that patients would be screened. A diagnosis of hypertension and the presence of albuminuria were each associated with increased use of an antiangiotensin agent.