Machaiah Madhrira

Ipilimumab granulomatous interstitial nephritis

Drug-induced interstitial nephritis is a recognized cause of acute and chronic renal failure. Some of them lead to the formation of granulomata. T-cell-mediated immune response is implicated in the pathogenesis. Here, we describe the case of a 74-year-old male patient with metastatic melanoma who was referred to our clinic with a history of rash and worsening renal function. Because of subacute onset, progressively worsening renal function in the presence of skin rash, elevated liver enzymes, and in the background of exposure, medication-induced interstitial nephritis was suspected. He received 3 doses of ipilimumab, a novel drug used in the treatment of metastatic melanoma within 3 months before the onset of renal failure. A renal biopsy was done, which showed granulomatous interstitial nephritis. Renal biopsy findings, temporal relation between renal failure and exposure to medication, and review of the literature supported a diagnosis of ipilimumab-induced renal failure. He was started on steroids, and renal function recovered in the next 1 month. Immune-related adverse reaction is one of the common side effects of ipilimumab. Ipilimumab-induced hepatitis and colitis has been previously reported in the literature. This is the first ever case report of ipilimumab-induced granulomatous interstitial nephritis.

Acute bilateral renal infarction secondary to cocaine-induced vasospasm

CASE PRESENTATION A 47-year-old African-American male with a history of hypertension for 1 year and cocaine use presented to the emergency department with acute onset of bilateral flank pain, nausea, vomiting, and diarrhea. Physical examination was unremarkable. Laboratory evaluation revealed a white blood count of 15.1 K/μl (normal 4.5-11.5 K/μl) and a serum creatinine of 2.4mg/100ml. A non-contrast CT scan of the abdomen was unremarkable. The patient was treated with morphine (for pain) and i.v. fluids, felt better, and was discharged for out-patient follow-up. The patient saw his primary care physician 2 days later (day 3) and reported persistence of the bilateral flank pain. The patient also reported a transient inability to urinate for 36 h before the visit. An abdominal ultrasound and blood chemistry were obtained. On day 5, he was referred by his physician to the emergency department for a serum creatinine of 9.2 mg/100 ml from day 3. At the time of admission, the patient reported using 5-6g/day of ibuprofen for the previous 4 days and admitted to sniffing cocaine a few hours before the initial onset of flank pain. On physical examination, the patient was a well-built African-American male with a temperature of 99.2 °F, pulse rate of 60/min, blood pressure of 150/85 mm Hg and weight of 85 kg (BMI 27.7 kg/m 2 ). There was no orthostasis, pallor, or skin rash. The heart and lung examinations were unremarkable. The abdomen was soft, with no suprapubic dullness. There was no costovertebral angle tenderness or pitting edema. The extremity pulses were symmetric and equal. Laboratory results are presented in Table 1. Serologic tests for hepatitis B and C viruses, human immunodeficiency virus, antinuclear antibody, and rheumatoid factor were negative. Serum complements, including C3, C4, and CH50, were within the normal range. Hemoglobin electrophoresis, chest X-ray, electrocardiogram, and echocardiogram were unremarkable. Renal ultrasound revealed normal-sized kidneys with mildly increased echogenecity and no hydronephrosis. A 99m Tc-MAG3 (mercaptoacetyltriglycine) radionuclide renogram showed multiple wedge-shaped photopenic areas in both kidneys (Figure 1a). Owing to the absence of a clear explanation for the patients acute renal failure, renal biopsy was performed 12 days after the onset of symptoms.

Effective ionic dialysance/blood flow rate ratio: an indicator of access recirculation in arteriovenous fistulae.

Effective ionic dialysance (EID) is an online measure of hemodialysis (HD) effective urea clearance that is calculated using changes in dialysate sodium conductivity. Effective ionic dialysance is blood flow (Qb) dependent. The presence of significant (≥5%) access recirculation (sAR) during dialysis lowers EID at a given Qb, thereby lowering EID/Qb. We propose using EID/Qb as a useful chairside tool for detection of sAR in arteriovenous fistulae (AVF). Data were collected from 47 patients with AVF (72% men, mean age 49 ± 11.8 years, duration on dialysis 3.78 ± 3.4 years, duration of fistula use 3.35 ± 3.42 years) dialyzed with an high-efficiency dialyzer with a mass transfer area coefficient (KoA) of 1714 ml/min. Effective ionic dialysance were measured at regular intervals by the Gambro Phoenix dialysis system during treatments. The access recirculation (AR) and access blood flow (Qa) were measured using the reference standard saline dilution technique (Transonic HD-02 monitor). Among the 323 HD sessions where Qb, EID, AR, and Qa were available, we identified 17 instances of sAR. The performance of EID/Qb as indicator of sAR was assessed by a receiver operator characteristic (ROC) curve (Stata version 10.1). The area under the ROC curve was 0.935 (95% confidence interval 0.869–1.000), which demonstrated a sensitivity of 76.5% and specificity of 96.4% at an EID/Qb ≤50% with a positive likelihood ratio of 21, negative likelihood ratio of 0.24, positive predictive value of 54.2%, and negative predictive value of 98.7%. We found similar test performance in patients who received HD with dialyzers with smaller surface areas and lower KoAs. The high specificity of EID/Qb makes it an excellent yet simple and early chairside indicator of AVF recirculation.

Membranous nephropathy with crescents associated with levamisole-induced MPO-ANCA vasculitis.

ANCA-associated vasculitis (AAV) is the most common cause of crescentic rapidly progressive glomerulonephritis (GN). Levamisole used as an adulterant in cocaine is increasingly recognized as a cause of AAV. We report the case of a 50 year old woman with atypical anti-MPO AAV associated with cocaine use and exposure to levamisole. In addition to the clinical and pathologic findings of crescentic GN, the patient also had biopsy evidence of secondary membranous nephropathy (MN). Although AAV and MN have been reported previously in the same patient and both have been induced by drug exposures, this is the first report of MN in a patient with AAV likely induced by levamisole. We suggest that MPO can cause both pauci-immune vasculitis and secondary membranous nephropathy in some cases, as in cases of levamisole-adulterated cocaine use.

Hemodialysis patients have plasmatic hypercoagulability and decreased fibrinolytic vulnerability: Role of carbon monoxide

Chronic hemodialysis is associated with significant thrombophilia. Of interest, hemodialysis patients have increased carboxyhemoglobin (COHb) and exhaled carbon monoxide (CO), signs of upregulated heme oxygenase (Hmox) activity. Given that CO enhances plasmatic coagulation, we determined whether patients requiring chronic hemodialysis had an increase in endogenous CO, plasmatic hypercoagulability and decreased fibrinolytic vulnerability. Carbon monoxide was determined by noninvasive pulse oximetry measurement of COHb. Blood samples were obtained just before hemodialysis. Thrombelastographic methods to assess plasma coagulation kinetics, fibrinolytic kinetics, and formation of carboxyhemefibrinogen (COHF) were used. Hemodialysis patients (n = 45) had abnormally increased COHb concentrations of 2.2 ± 1.9%, indicative of Hmox upregulation. Coagulation and fibrinolytic parameter normal values were determined with normal individual (n = 30) plasma. Thirty-seven patients of the hemodialysis cohort had COHF formation (82.2%, [67.9%–92.0%]; mean, [95% confidence interval]), and many of this group of patients had abnormally great velocity of clot growth (73.3%, [58.1%–85.4%]) and strength (75.6%, [60.5%–87.1%]). Furthermore, over half of COHF positive patients had a hypofibrinolytic state, evidenced by an abnormally prolonged time to maximum rate of lysis (53.3%, [37.9%–68.6%]) and clot lysis time (64.4%, [48.8%–78.1%]). Carbon monoxide enhanced coagulation and diminished fibrinolytic vulnerability in hemodialysis patients. Future investigation of hemodialysis, CO-related thrombophilia is warranted.

Outcome of patients on combined extracorporeal membrane oxygenation and continuous renal replacement therapy: a retrospective study

Background Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy used in the management of cardiopulmonary failure. Continuous renal replacement therapy (CRRT) is often added to the treatment for the correction of fluid and electrolyte imbalance in patients with acute kidney injury. Most of the literature on the use of combined ECMO and CRRT has been on pediatric patients. There are limited outcome data on the use of these combined modalities in adult patients. Methods This is a retrospective analysis of all the patients above the age of 18 years who underwent combined ECMO and CRRT at a tertiary care medical center during the period January 2007 to January 2012. The primary outcomes measured were mortality at one year and renal recovery or dialysis dependence at one month. Results A total of 40 patients who were treated concurrently with ECMO and CRRT were identified. The mean age was 47.01 ± 18.29 years. The most common indications for initiation of CRRT were combined fluid overload and electrolyte imbalance. Mortality at one month was (32/40) 80%. Among the 8 survivors (20%), 3 patients required continuation of hemodialysis and 5 patients were independent of dialysis at 30 days. Conclusions Mortality of patients treated with combined ECMO and CRRT is high. Initiation of CRRT in these patients is simply an indicator of severity of illness and fatality. Younger age, higher arterial pH, left ventricular dysfunction and use of VA ECMO are associated with improved survival in these patients.

Graft and Patient Survival

Kidney transplantation is agreed upon as the best treatment available for most patients with end-stage renal disease (ESRD). It not only improves quality of life (Am J Kidney Dis 15(3):201–8, 1990; Kidney Int 50(1):235–42, 1996; N Engl J Med 28;312(9):553–9, 1985; Transplantation 54(4):656–60, 1992) of our patients and reduces medical expense (Kidney Int 50(1):235–42, 1996; Semin Nephrol 12(3):284–9, 1992) but also has shown to be a life-prolonging procedure. Multiple studies using renal transplant recipients with dialysis patients have found that patient survival is clearly better with renal transplantation than with dialysis (Kidney Int 21(1):78–83, 1982; Transplantation. 60(12):1389–94, 1995; Nephrol Dial Transplant 12(8):1672–9, 1997; Kidney Int 53(3):767–72, 1998).

Early Posttransplant Isolated v1 Lesion Does Not Need to Be Treated and Does Not Lead to Increased Fibrosis

Acute vascular rejection (AVR) is characterized by intimal arteritis in addition to tubulitis and interstitial inflammation. It is associated with a poorer prognosis compared to tubulointerstitial rejection (AIR) and AVR is associated with a higher rate of graft loss than AIR. The prognosis and treatment of arteritis without tubulitis and interstitial inflammation (isolated v1 lesion) are still controversial. We report a case of a patient who had a biopsy of the kidney allograft for evaluation of slow graft function. The biopsy revealed an isolated v1 lesion. However, we chose not to augment immunosuppression. The patients kidney allograft function improved over time with close monitoring. Repeat biopsy a year later showed no evidence of endothelialitis and relatively unchanged fibrosis and no other abnormalities. Although it is suggested that most cases of isolated v1 lesions will respond to corticosteroids or T cell depleting therapies, some cases will improve with conservative management. Further studies are needed to determine which cases could be managed conservatively.

Idiopathic Nonviral Cryoglobulinemia Treated Successfully With Rituximab.

Cryoglobulinemia is a systemic inflammatory syndrome that generally involves small-to-medium vessel vasculitis due to cryoglobulin-containing immune complexes. The therapeutic management of idiopathic cryoglobulinemic vasculitis has yet to be defined because no study has evaluated the best strategies. However, treatment of severe vasculitis is traditionally based on a combination of corticosteroids and immunosuppressants or plasmapheresis, and more recently rituximab. We report a case of 77-year-old female patient diagnosed with idiopathic cryoglobulinemia, treated successfully with 6 months prednisone tapering and 2 doses of rituximab (1 g each dose). After receiving the above-mentioned treatment, her creatinine went back to normal with resolution of proteinuria and hematuria, normalization of serum complements, and significant improvement in her clinical picture. We conclude that rituximab could be an effective treatment for idiopathic cryoglobulnemia.

Allergic Interstitial Nephritis Manifesting as a Striated Nephrogram

Allergic interstitial nephritis (AIN) is an underdiagnosed cause of acute kidney injury (AKI). Guidelines suggest that AIN should be suspected in a patient who presents with an elevated serum creatinine and a urinalysis that shows white cells, white cell casts, or eosinophiluria. Drug-induced AIN is suspected if AKI is temporally related to the initiation of a new drug. However, patients with bland sediment and normal urinalysis can also have AIN. Currently, a definitive diagnosis of AIN is made by renal biopsy which is invasive and fraught with risks such as bleeding, infection, and hematoma. Additionally, it is frequently unclear when a kidney biopsy should be undertaken. We describe a biopsy proven case of allergic interstitial nephritis which manifested on contrast enhanced Magnetic Resonance Imaging (MRI) as a striated nephrogram. Newer and more stable macrocyclic gadolinium contrast agents have a well-demonstrated safety profile. Additionally, in the presentation of AKI, gadolinium contrast agents are safe to administer in patients who demonstrate good urine output and a downtrending creatinine. We propose that the differential for a striated nephrogram may include AIN. In cases in which the suspicion for AIN is high, this diagnostic consideration may be further characterized by contrast enhanced MRI.