Rapid Improvement Of Renal Function Research Articles

Efficacy and Safety of Daratumumab in Combination with Bortezomib, Thalidomide, and Dexamethasone Regimens in Newly Diagnosed Multiple Myeloma with Renal Insufficiency in Real-World: A Non-Interventional Prospective Multicenter Observational Study

Background: Renal impairment (RI) is one of the common serious complications of MM. The DARE Phase 2 clinical study is daratumumab-based regimen for the treatment of MM patients with renal insufficiency, which is designed to use daratumumab in combination with dexamethasone for the treatment of RRMM with severe renal insufficiency. According to the updated data, after 8.3 months of follow-up, the 6-month PFS rate was 48.6%, ORR was 41.4%, renal response rate (RRR) was 20.7%. CASSIOPEIA phase III clinical study showed that with the extension of treatment time, the sCR rate and minimal residual disease (MRD) negative rate in D-VTd group were significantly improved compared with those in VTd group. According to the evidence from previous large phase III clinical trials of daratumumab in NDMM as well as its DARE phase II study and clinical case reports, daratumumab based treatment has a rapid onset of action in the treatment of MM patients with severe renal insufficiency, effectively response to the disease and improve the renal function of patients. An observational, multi-center, non-interventional study was designed to evaluate the safety and efficacy of daratumumab in combination with VTD in NDMM patients with renal dysfunction in real-world clinical practice. (NCT 05561049) Methods:NDMM patients older than 18 years and with a glomerular filtration rate(eGFR) of less than 40 ml/min were enrolled. Patients received VTD for C1, then go to DaraVTD for C2-4. The dose of Daratumumab was 16 mg/kg I.V. every week for 2cycles(cycles 2-3) , 16 mg/kg I.V. every 2 weeks for one more cycles;“Thalidomide”: 100 mg, P.O., Days 1-28/1-4 cycles;“Bortezomib”: 1.3 mg/m2, SC, Days 1, 4, 8, 11/1-4 cycles; Dexamethasone: 20-40mg, PO/I.V., qw/1-4 cycles. After induction therapy, patients entered consolidation therapy. Transplant eligable patients undergo stem cell collection and autologous stem cell transplantation followed by consolidation with DVTd regimen for 2 more cycles. Four more cycles of consolidation with DVTd were performed in transplant ineligible patients. The primary endpoint of this study is to evaluate VGPR+ rate after consolidation. The secondary endpoint is ORR, renal response rate (RRR), CR rate, MRD negativity after consolidation, and DOR, PFS, OS. NCI CTCAE V5.0 criteria were used to evaluate adverse events. Result: From Jan 1th to June 30 th 2023, 23 patients were enrolled. The median age of these 23 patients was 64 (34-78), 69.6%(16/23) was male.(Table 1) Among the 18 patients who have had response evaluation, the ORR was 94.4%. median onset time of response was 2 months. After induction therapy, the ORR was 100%, 50% patients had gotten CR. After consolidation, All patients were above VGPR and CR and were NGS MRD negative.55.5% patients(10/18) achieved renal remission after one cycle, while 86.7% after 2 cycles, 91.7% after 3 cycles and 100% after 4cycles. Among the 20 patients who have had adverse events evaluation. The main treatment-related adverse events were hematological toxicity, including neutropenia (n=10/20, grade 1-2 for 6 pts and grade 3-4 for 4 pts), lymphopenia (n=5/20, grade 1-2 for 5 pts) and thrombocytopenia (n=8/20, grade 1-2 for 6 pts and grade 3-4 for 2 pts). One patient with acute pancreatitis had to stop treatment. Other toxicities to date included pneumonia (n=5/20, grade 1 for 4 pts and grade 2 for 1 pts), peripheral neuropathy (n=10/20, grade 1 for 7 pts and grade 2 for 3 pts), and rash(n=5). The infusion related reactions were 37.5%(n=6/18, grade 1 for 4 pts and grade 2 for 2 pts). Conclusion: In Chinese NDMM patients with RI, quad-drug induction of DVTD with/without ASCT consolidation showed nice tolerability and high overall response of disease even with a high percentage of high-risk patients. This preliminary study also suggested excellent efficacy with rapid improvement in renal function. The most common adverse events were hematological toxicity. Updated results will be presented at the following phase.

Atypical HUS in a Lung Transplant Recipient with Salmonellosis

<h3>Introduction</h3> Thrombotic microangiopathy/Atypical HUS following lung transplantation is unusual. An unusual case of TMA with multiple possible etiologies, including infection, is presented. <h3>Case Report</h3> 64-year-old African American woman 2 years post right single lung transplant presented with shortness of breath, lethargy and diarrhea. Infectious work up revealed MRSA in BAL and Salmonella in stool by PCR. She was treated with Vancomycin and Levaquin. Her immunosuppression regimen consisted of prednisone, Tacrolimus and Mycophenolate. Tacrolimus levels were within normal range (5-8 ng/ml). The platelet count started to decline on day 5 of hospitalization, with a nadir of 74K. She was also noted to have worsening renal function with creatinine increasing. There was evidence of hemolytic anemia. ADAMTS-13 activity was normal. Renal Biopsy was performed: There were arteriolar and glomerular capillary thrombi associated with intimal edema and endothelial injury. Ischemic glomerular changes were notes as was acute tubular injury. The findings were interpreted as thrombotic microangiopathy. There was no evidence of myoglobin casts. Therapy included transitioning calcineurin inhibitor to Cyclosporine and continued antibiotic therapy. Due to rapid improvement of renal function, Plasmapheresis was not performed. <h3>Summary</h3> Atypical HUS is a very unusual cause of AKI in salmonellosis, felt to relate to S.Typhi virulence factors. Cases of CNI induced atypical HUS have also been reported in lung transplant recipients, with an annual incidence of 2.3%. Early recognition is important in regards to prognosis and survival. In summary, regardless of etiology, is vital to recognize clinical features of atypical HUS/TTP early in transplant recipients and to clinically evaluate for many possibly etiologic factors before directly attributing injury solely to CNI related endothelial injury, as documented in this clinical case.

Vitamin B12 deficiency-induced pseudothrombotic microangiopathy without macrocytosis presenting with acute renal failure: a case report

BackgroundVitamin B12 deficiency-induced thrombotic microangiopathy, known as pseudothrombotic microangiopathy, is a rare condition which resembles the clinical features of thrombotic thrombocytopenic purpura but requires a markedly different treatment. Most cases of vitamin B12 deficiency have only mild hematological findings, but in approximately 10% of patients life-threatening conditions have been reported.Case presentationWe report a case of a 46-year-old Moroccan man presenting with severe hemolytic anemia, thrombocytopenia, and renal failure in absence of macrocytosis, thus mimicking a genuine thrombotic thrombocytopenic purpura. Rapid improvement of renal function observed with only hydration and transfusions of packed red blood cells and the presence of pancytopenia suggested a bone marrow deficiency associated to a hemolytic component of unclear origin. Detection of low levels of vitamin B12 and rapid restitutio ad integrum with its replacement supported the diagnosis of pseudothrombotic thrombocytopenic purpura caused by vitamin B12 deficiency.ConclusionsDiagnosis of pseudothrombotic thrombocytopenic purpura caused by vitamin B12 deficiency might be difficult. Awareness of clinicians toward this differential diagnosis might spare patients from unnecessary therapeutic plasma exchange that is burdened by morbidity and mortality.

Atheroembolic Renal Disease: A Beneficial Effect of Steroids

Atheroembolic renal disease (AERD) or cholesterol crystal embolisation often is an under diagnosed clinical illness. It is a multisystemic disease with progressive renal failure due to foreign body reaction of cholesterol crystals flushed into a small vessel system of the kidneys from the arteriosclerotic plaques. It usually occurs after vascular catheterization, anticoagulation and less frequently spontaneously. Renal and patient prognosis are usually poor. We hereby are reporting a case report of a 62-year-old male patient with dyslipidemia who underwent percutaneous coronary intervention for unstable angina and consecutive AERD with typical clinical appearance few days after the event. Rapid improvement of renal function was noticed after treatment with systemic corticosteroids.

Rapid improvement of renal function in patients with acute pulmonary embolism indicates favorable short term prognosis

ObjectiveVarious clinical and biochemical parameters predict the prognosis of patients with acute pulmonary embolism(APE). Treatment of APE can improve a patient's hemodynamic status, restoring adequate peripheral organ perfusion. Therefore, we hypothesized that improvement of renal function can predict short term prognosis of APE patients. Material & MethodWe evaluated 232 consecutive patients (94men,aged 67±18years) with APE proven by spiral computer tomography. Blood samples were collected for creatinine assays on admission and 72hours later, the glomerular filtration rate(eGFR) was estimated using the MDRD formula. ResultsDuring the first 72hours, 6 subjects died, while during the first 30days 24(10%) subjects died (APE mortality 8%). On admission eGFR<60ml/min was present in 113 patients(49%) and after 72hours in 85 patients(38%). In 26 patients(11%) eGFR on admission was <60ml/min and renal function did not improve during subsequent 72hours. In this group the 30-day all-cause and APE-related mortality rates were 27% and 23%, respectively, while serious adverse events occurred in 38% of them. 206 patients with eGFR>60ml/min showed a more favorable prognosis (8% 30-day all-cause mortality) than subjects with eGFR<60ml/min and a stable eGFR during the first 72hours (27% mortality rate, p<0.003). Persistent renal dysfunction predicted all-cause and PE-related 30-day mortality (hazard risk 2.53(CI95%:0.96-6.68),p=0.06 and 3.04(CI95%:1.28-7.26),p=0.01, respectively). ConclusionApproximately 50% of patients with APE have at least a moderately impaired renal function on admission. Renal function improves within 72hours in patients with a good prognosis, while “persistent” renal dysfunction indicates an increased mortality.

Accelerated recovery from nephrotic syndrome with acute renal failure by double filtration plasmapheresis in a patient with lupus podocytopathy

We describe a case of an adult female who presented with nephrotic syndrome. She was diagnosed with systemic lupus erythematosus with serum antinuclear antibodies, leucopenia with lymphopenia, butterfly erythema, and nephrotic syndrome. Renal biopsy revealed normal glomeruli with diffuse effacement of the foot processes, consistent with lupus podocytopathy. Although human albumin replacement was performed initially, acute renal failure developed rapidly. Therefore, she was treated with double filtration plasmapheresis (DFPP) in addition to oral steroid. After steroid therapy combined with DFPP, the renal function and proteinuria improved rapidly. Although the impact of DFPP on the treatment of lupus nephritis remains to be delineated, our observations suggest that DFPP in lupus podocytopathy played a pivotal role in facilitating the early recovery from renal injuries. Because of the rapid improvement of renal function without any change in body weight by DFPP, acute renal failure in the setting of lupus podocytopathy might contribute to an alternative pathophysiological factor for the diminished glomerular filtration rate, similar to that observed in the setting of idiopathic minimal change glomerulopathy.

ステロイド療法により進行を抑えることができたChinese Herbs Nephropathyの1例

The patients was a 43-year-old woman whose chief complaints were nausea and heaviness of the heads. There was a history of toxemia of pregnancy. The patient had previously taken Tenshin Tokishigyaku-ka-goshuyu-shokyo-to for two years because of cold sensitivity. Fever, thirst, and loss of appetite developed from approximately 18 months after she started treatment with the Chinese herbal preparation, and she presented at our outpatient clinic 2.5 years later. On initial examination, deterioration of renal function was evident and the serum creatinine level was 3.4 mg/dl. A renal biopsy specimen showed marked interstitial fibrosis without inflammatory cell infiltration, leading to the diagnosis of Chinese herbs nephropathy (CHN). Steroid therapy was started on the 36th hospital day after a sharp rise in the serum creatinine level to 5.1 mg/dl. This resulted in the rapid improvement of renal function and reduction of the serum creatinine to 2.6 mg/dl by 8 weeks after the initiation of treatment. In a study on the use of steroids for patients with progressive moderate renal dysfunction caused by Chinese herbs, Vanherweghem et al. reported that the progression of renal failure was appreciably slowed in patients given steroids when compared with the control group. We were also able to slow the progression of renal dysfunction in our patient by steroid therapy, although the prognosis of CHN is generally considered to be very poor.

Reversibility of Renal Failure in Newly Diagnosed Patients with Multiple Myeloma and the Role of Novel Agents.

Abstract 955Renal impairment (RI) is a common complication of multiple myeloma (MM) and is associated with increased mortality. High dose dexamethasone-based regimens have been extensively used for the initial management of patients with MM presenting with RI. Recently, novel agent-based regimens have been introduced in the frontline management of MM. The purpose of our analysis was to assess the effect of novel agent-based regimens on the rate of RI improvement and compare their efficacy with conventional chemotherapy (CC) plus dexamethasone (Dexa) in newly diagnosed MM patients. Over the last decade, 82 patients with newly diagnosed MM and RI, defined as creatinine clearance (CrCI) <50ml/min, received frontline treatment in our Center. Patients were divided into three groups: group A: 28 patients who received CC plus Dexa-based regimens (VAD, VAD-like regimens, melphalan plus Dexa); group B: 38 patients who received IMiDs-based regimens (thalidomide or lenalidomide with high dose Dexa and/or cyclophosphamide or melphalan) and group C: 16 patients who received bortezomib-based regimens with Dexa. Renal complete response (RCR) was defined as a sustained increase of baseline CrCI to >60ml/min. Renal partial response (RPR) was defined as an increase of CrCI from<15 to 30-50ml/min. Renal minor response (RMR) was defined as sustained improvement of baseline CrCI of<15ml/min to 15-29 ml/min, or, if baseline CrCI was 15-29 ml/min, improvement to 30-59 ml/min. Patients in group B were older than those of groups A and C (p=0.01) while more patient in group C had light chain only MM than in groups A and B (p=0.04). There were no significant differences in the severity of RI, Bence Jones proteinuria, hypercalcemia or ISS stage among the three groups. Improvement of renal function, recorded as RMR or better, was achieved more frequently in patients treated with novel agents (group B: 87% and in group C: 94%) than in patients treated with CC plus Dexa-based regimens (64%, p=0.024). Among 9 patients who required renal dialysis 3 became independent of this procedure after treatment. We subsequently focused our analysis in major renal responses (RPR or RCR), because this endpoint is clinically more relevant. RCR was achieved in 43% of patients in group A, in 50% in group B and in 69% of patients in group C (p=0.2) and RCR+RPR rates were 50% and 57% and 81% for groups A, B and C respectively (p=0.1). Creatinine clearance <30 ml/min was associated with a significantly lower probability of RCR or RPR only in patients treated with CC plus Dexa- or with IMiDs-based regimens (p<0.01), but not in patients treated with bortezomib (p=0.529). The probability of RPR+RCR was similar for patients treated with IMiDs compared to CC plus Dexa-based regimens (p=0.619). In multivariate analysis bortezomib–based regimens (p=0.02, OR: 7, 95% CI 1.5-25) and CrCl>30 ml/min (p=0.002, OR: 6.1, 95% CI 2.5-22.5) were independently associated with a higher probability of RCR+RPR. The median time to RPR was similar for patients treated with IMiDs compared to CC plus Dexa-based regimens (2.2 months for Group A, 1.5 months for Group B, p=0.587) but it was significantly shorter for Group C (0.7 months, p=0.017). Other factors associated with a shorter time to ≥RPR included CrCl>30 ml/min (p=0.039) and age<75 (p=0.089). In multivariate analysis bortezomib–based regimens (p=0.004, OR: 3 95% CI 1.6-6.7) and CrCl>30 ml/min (p=0.006, OR: 2.5 95% CI 1.3-4.5) were independently associated with a shorter time to ≥RPR. In landmark analysis (time was one month in order to reduce bias due to early deaths), rapid improvement of renal function (≤1 month) was associated with a trend for a longer survival compared to patients who achieved renal response later (>1 month) (47 vs. 21 months, p=0.19). Myeloma response to treatment was 58%, 68% and 79% for the three treatment groups respectively and was associated with renal response (p=0.024), though less strongly with a major renal response (p=0.061). Our data indicate that novel agent-based regimens can improve renal function in most patients; furthermore bortezomib-based regimens improve renal function to a higher degree and significantly more rapidly than CC plus Dexa-based or IMiD-based regimens even in patients with severe renal impairment. We conclude that bortezomib-based regimens may be the preferred treatment for newly diagnosed myeloma patients who present with renal impairment. Disclosures:Dimopoulos:JANSSEN-CILAG: Honoraria; CELGENE: Honoraria.

Linezolid-Associated Acute Interstitial Nephritis and Drug Rash With Eosinophilia and Systemic Symptoms (DRESS) Syndrome

Linezolid is a recent addition to the antibiotic armamentarium against Gram-positive bacteria, including multiresistant staphylococci and enterococci. Linezolid is relatively well tolerated and is not believed to be nephrotoxic. However, we report the case of an 88-year-old woman who was treated for prosthetic joint infection and methicillin-resistant Staphylococcus aureus bacteremia with vancomycin followed by linezolid therapy. On day 7 of linezolid treatment, the patient developed severe pruritus, macular rash, facial edema, eosinophilia, marked increase in serum creatinine level, and mild hepatitis. Renal biopsy showed acute interstitial nephritis with eosinophilic cells. Discontinuation of linezolid and a short course of prednisone led to rapid improvement of renal function. This case of linezolid-associated acute interstitial nephritis within the context of a drug rash with eosinophilia and systemic symptoms (DRESS) syndrome in a patient treated with linezolid raises concerns about the presumed renal safety of this drug. Clinicians should be aware of this potential life-threatening adverse reaction and monitor kidney function while patients are using linezolid.

Elucidation of Acute Renal Failure Due to Recurrent Non-Hodgkin Lymphoma by F-18 FDG PET/CT

Abstract:Renal impairment secondary to lymphomatous parenchymal infiltration is uncommon. Early recognition of this cause of acute renal failure (ARF) is important as initiation of steroid therapy often results in rapid improvement in renal function. We highlight the usefulness of the functional asp

Treatment of Patients with Multiple Myeloma Complicated by Renal Failure with Bortezomib - Based Regimens.

Introduction: Renal failure is a common feature of multiple myeloma and a major management problem. There is limited data regarding the reversibility of renal failure, the kinetics of serum creatinine and the safety of novel agents, such as bortezomib, when administered to newly diagnosed or relapsed/refractory patients with renal failure. The purpose of our analysis was to assess the frequency of renal failure improvement and kinetics of serum creatinine in patients who received bortezomib-based regimens.Patients and methods: We evaluated 20 consecutive patients with newly diagnosed (n=7) or relapsed/refractory (n=13) multiple myeloma and renal failure, defined as a serum creatinine ≥ 2mg/dl. Patients' median age was 66 years (range 43–88 years). Median serum creatinine was 3.8 mg/dl (range 2–11.9 mg/dl) and median creatinine clearance was 15.3 ml/min (range 6.4–33.3). Other features included hemoglobin <10gr/dl in 12 patients, platelets <100 × 109/l in 3 patients and elevated serum LDH in 9 patients. All patients received bortezomib plus dexamethasone alone or in combination with other agents, such as thalidomide, doxorubicin or melphalan. Reversibility of renal failure was defined as a sustained decrease of serum creatinine to <1.5 mg/dl and renal response was defined as ≥50% decrease of serum creatinine from its peak value.Results: Reversal of renal failure was documented in 35% of all patients and the median time to reversal was 23 days. Moreover, 9 patients (45%) had 50% decrease in serum creatinine and the median time to decrease was 34 days. Some decrease of creatinine was documented in 88% of patients. Among four patients who were on renal dialysis, 2 became independent of this procedure after the second and the third cycle of treatment. The objective response rate was 61% and the median progression free survival for responders was 12 months. Toxicities were similar to those seen in myeloma patients without renal failure who were treated with bortezomib-based regimens. Grade 3–4 neutropenia and thrombocytopenia were seen in 28% and 22% of patients respectively. One patient died of infection and bortezomib had to be discontinued in 4 patients due to grade III neurotoxicity.Conclusions: When bortezomib-based regimens are administered to myeloma patients with renal impairment their toxicity and efficacy are similar to those observed in patients with normal renal function. Moreover, these regimens are associated with rapid improvement of renal function in most patients and with reversal of renal failure in one-third of them.

Maladie de Kimura associée à une glomérulonéphrite extra-capillaire nécrosante

Kimura's disease is a rare and benign chronic inflammatory soft-tissue disorder of unknown origin. Most cases involve young Asian males. The typical presentation consists of painless papules or nodules with a predilection for the head and neck region, associated with lymphadenopathy, parotid gland involvement, peripheral blood eosinophilia and raised immunoglobulin E. A 49-year-old Mauritian man was hospitalized for nephrotic syndrome. Examination revealed a painless 3 cm nodule in the left pre-auricular region and multiple enlarged left cervical lymph nodes. Histopathologic examination of a nodule confirmed the diagnosis of Kimura's disease, which was associated with necrotic extracapillary glomerulonephritis. Corticosteroids were initiated, resulting in rapid improvement of renal function and partial regression of the patient's cutaneous nodules and lymph node disorder. Renal manifestations are the only visceral localization of Kimura's disease, and proteinuria is seen in 12% of cases, of which 50% are accompanied by nephrotic syndrome. Many different histologic types of renal involvement may be observed with potentially severe lesions. To our knowledge, this is the first case of Kimura's disease associated with extracapillary glomerulonephritis.

Catheter-directed Thrombectomy and Thrombolysis for Acute Renal Vein Thrombosis

To evaluate the technical success and clinical outcome of the percutaneous treatment of acute renal vein thrombosis (RVT). Retrospective review was conducted of all patients with acute RVT treated with percutaneous catheter-directed thrombectomy with or without thrombolysis at one institution between 2000 and 2004. Demographics, comorbid conditions, and clinical outcomes associated with therapy were assessed. Seven thrombosed renal veins in six patients (mean age, 51.5 +/- 18.8 years) were treated with percutaneous catheter-directed thrombectomy/thrombolysis. Thrombosed renal veins included two allografts and five native veins, and diagnosis was confirmed in all cases by direct renal venography. Inferior vena cava thrombosis was the cause of RVT in one patient, and glomerulopathy was the cause in the remaining patients. Percutaneous mechanical thrombectomy was performed in all cases, and five renal veins were additionally treated with thrombolysis for a mean duration of 22.1 +/- 21.0 hours. Restoration of flow to renal veins was achieved in all thrombosed renal veins. Clinical improvement occurred in all patients: the mean serum creatinine level improved from a preoperative level of 3.3 +/- 1.92 mg/dL to a postoperative level of 1.92 +/- 1.32 mg/dL (P = .008). Mean glomerular filtration rate improved from a preoperative level of 30.8 +/- 23.0 mL/min per 1.73 m(2) to 64.2 +/- 52.4 mL/min per 1.73 m(2) (P = .04). There were no pulmonary emboli or hemorrhagic complications, and no RVT recurrence was documented during a median follow-up of 22.5 months. Percutaneous catheter-directed thrombectomy with or without thrombolysis for acute RVT is associated with a rapid improvement in renal function and low incidence of morbidity. It is feasible for native and allograft renal veins and should be considered in patients with acute RVT, particularly in the setting of deteriorating renal function.

Rituximab treatment for glomerulonephritis in HCV-associated mixed cryoglobulinaemia: efficacy and safety in the absence of steroids

Rituximab, an anti-CD20 monoclonal antibody, has been used in lupus nephritis and membranous idiopathic nephropathy and has proved effective in non-renal manifestations of type II mixed cryoglobulinaemia (MC) syndrome. We investigated the possible efficacy and safety of rituximab in the treatment of cryoglobulinaemic nephritis. Five patients with active, biopsy-proven, glomerulonephritis in hepatitis C virus (HCV)-related type II MC syndrome were treated with four weekly infusions of rituximab (375 mg/m2) in monotherapy, without steroids whenever possible. Rituximab was the first-line therapy in three cases. A rapid and sustained renal response was observed in all patients, in one of them without retreatment up to the last follow-up (month 21+). Renal biopsy was repeated after 6 months in one patient and histopathological improvement was documented. Three patients relapsed, at months +5, +7 and +12 of follow-up, respectively. Two of them were then retreated with rituximab and again presented a rapid improvement in renal function. Maintenance therapy with rituximab was performed in two patients: nephritis remission was maintained in both. Fc-gamma receptor 3a (FcgammaRIIIa) genotype characterization was consistent with the clinical response observed. Rituximab also proved effective against other active MC manifestations, when present. No major side-effects occurred and steroids were not required in the follow-up. Rituximab may provide effective and safe therapy in type II MC-related glomerulonephritis, possibly as first-line therapy, avoiding steroids and hazardous immunosuppressive treatment.

Acute renal failure and severe neurotoxicity following valacyclovir

The l-valyl ester of acyclovir is generally well tolerated. Elderly patients and those with chronic renal failure are most susceptible to adverse effects involving the central nervous system. Renal failure associated with neurotoxicity following valacyclovir is generally reported among patients with preexisting impaired renal function [1, 2, 3, 4]. A 62-year-old, 65-kg, posttraumatic paraplegic woman with limited upper limb movement and bladder dysfunction complained of chest pain followed by thoracic vesicular rashes. Her general practitioner prescribed valacyclovir 1 g three times a day. Apart from her disability she was healthy and her past medical history was unremarkable. Four days later the patient was admitted to the general medical ward because of progressive altered mentation, with a Glasgow Coma Scale of 10 (E2 V3 M5). She was stuporous and oliguric but heart rate, arterial pressure, temperature, and arterial blood gases were normal. Common laboratory tests were also normal except for urea nitrogen at 56 mg/dl (normal 10–50 mg/dl) and creatinine at 1.8 mg/dl (normal 0.6–1.1 mg/dl). Valacyclovir therapy was maintained. Neither cerebral computed tomography, without contrast medium, nor abdominal ultrasound examination revealed any abnormalities. The next day urea nitrogen was 71 mg/dl, creatinine 2.6 mg/dl, and her neurological condition further worsened (E2 V1 M3), but a encephalic computed tomography without radiocontrast was again negative. She was therefore admitted to our ICU, intubated, and mechanically ventilated. Electroencephalography showed a nonconvulsive epileptic status, and phosphenytoin treatment was started. A lumbar puncture was performed to rule out meningoencephalitis, but no microorganisms were seen on a Gram stain. Cultures of cerebrospinal fluid, blood, and urine were also negative. Diuresis during the first 24 h was 3.8 l, and she remained polyuric throughout her ICU stay. Antiviral therapy was finally stopped. Twenty-four hours after discontinuation of valacyclovir there was a rapid improvement in renal function and her Glasgow Coma Scale rose to 9 (E3 Vt M5). The patient was extubated 2 days later with full neurological recovery and was discharged from the ICU, with creatinine concentration of 0.7 mg/dl and nitrogen of 17 mg/dl. The altered mentation, confusion and coma in our case aere consistent with the typical findings of acyclovir neurotoxicity [5]. The absence of fever, focal neurological deficits, and signs of lateralization on electroencephalography, along with normal results of cerebrospinal fluid analysis and cerebral computed tomography, generally aid in ruling out viral encephalitis. Unfortunately a baseline serum creatinine concentration was not obtained in our patient before hospital admission, but the temporal relationship between the initiation of valacyclovir and the onset of adverse effects strongly implicate valacyclovir as the cause of patient’s worsening and suggests that acute renal failure and coma can occur early. Furthermore, 4 days after ICU admission serum creatinine concentration and nitrogen were normal (0.7 and 17 mg/dl). Due to fear of herpes zoster encephalitis valacyclovir administration was maintained without dose adjustments despite the progressive impairment of renal function in presence of a brisk, but deceptive, urinary flow. In conclusion, valacyclovir can also impair renal function in elderly patients without preexisting renal failure and, without appropriate dose reduction, can induce life-threatening neurotoxicity.

Sirolimus rescue of renal failure in children after combined liver-kidney transplantation

Calcineurin inhibitors (CNI) are the main immunosuppressive drugs in solid organ transplantation. However, their use is hampered by side effects like nephrotoxicity. We report an exceptional experience with three children treated with sirolimus after combined liver and kidney transplantation with prolonged renal failure and CNI-associated nephrotoxicity. Two girls experienced prolonged renal graft failure after combined liver-kidney transplantation for 11 and 12 weeks. Repeated biopsies did not show any rejection but did exhibit tubular damage and acute CNI-toxicity. A boy with hyperoxaluria after liver and (a third) renal transplantation experienced acute renal graft failure after an early steroid-resistant rejection. All children were switched to sirolimus-based immunosuppression and cessation of CNI therapy, which was followed by rapid improvement of renal function. Rejection of liver or kidney did not occur after CNI withdrawal. Sirolimus was commenced with 3 mg/m2/day in two doses and resulted in reasonable drug exposure. However, drug monitoring was required to adjust sirolimus dosage. Prolonged renal failure after transplantation with severe CNI toxicity may be salvaged successfully with sirolimus-based immunosuppression.

Calcineurin inhibitor nephrotoxicity: reduction in dose results in marked improvement in renal function in patients with coexisting chronic allograft nephropathy.

Calcineurin inhibitors (CNI) have significantly reduced the incidence of acute rejection. Nephrotoxicity however, may contribute to long-term allograft dysfunction. Forty-six biopsies from patients who had been transplanted for more than 6 months were examined. Sixteen biopsies had evidence of chronic allograft nephropathy (CAN) alone, 21 biopsies had evidence of coexisting CAN in addition to histological evidence of calcineurin inhibitor nephrotoxicity (CNIN) while nine had neither evidence of nephrotoxicity nor CAN. Patients with evidence of nephrotoxicity underwent a reduction in dose of CNI while those with CAN alone had no change in therapy. Renal function was followed for a mean of 17.4 months after biopsy. The serum creatinine at the time of diagnostic renal biopsy was comparable between those with CAN alone (mean 0.25 +/- 0.18 mmol/L) and those with coexisting CNIN (mean 0.23 +/- 0.05 mmol/L, p=0.33). The patients with CNIN however, had a rapid improvement in renal function within 1 month after dose reduction. This was sustained for the duration of follow-up (mean serum creatinine 0.162 +/- 0.038 mmol/L at 1 yr after dose reduction; p=0.001). In comparison, those with CAN alone had a gradual decline in renal function with a serum creatinine at 1 yr after biopsy of 0.31 +/- 0.187, p=0.01. Reduction in the dose of CNI in those with histological evidence of nephrotoxicity resulted in a sustained improvement in renal function.

Les manifestations rénales de la sarcoïdose. à propos de neuf observations

Clinical renal involvement in sarcoidosis (report of nine cases). Purpose. — Clinical renal outbreaks occurring in the course of sarcoidosis are polymorphous. Methods. — Nine patients presenting with sarcoidosis were followed up for 18 years. Results. — Five patients presented with chronic interstitial nephritis. Renal failure accompanying granuloma was also present in three of them. Corticotherapy allowed rapid improvement in renal function in three patients. In two other cases, late treatment prevented recovery and led to end-stage renal failure in one case. In another case, persistent hypercalciuria was responsible for bilateral nephrolithiasis further treated via extracorporeal lithotrity. One case of mesangial glomerulonephritis and two morbid associations (retroperitoneal fibrosis and Henoch-Schönlein purpura) were observed. Conclusion. — Interstitial nephritis is still a severe clinical renal outbreak. Corticotherapy must be prescribed early to avoid renal failure. Calcium metabolism disorders are frequent and often combined with interstitial nephritis. Hypercalcemia can often and rapidly be improved via corticotherapy, while monitoring of hypercalciuria proves to be more difficult. Membranous glomerulonephritis is still the most frequently reported glomerular lesion.

Analysis of risk factor for patients and renal survival in anti-myeloperoxidase antibody (MPO-ANCA) associated glomerulonephritis

We investigated the clinical and histological features and the outcome of 15 patients with antimyeloperoxidase antibody(MPO-ANCA) associated glomerulonephritis. The patients were divided into two groups on the basis of renal functional outcome: Group 1 consisted of 7 patients where an initial deterioration in renal function was improved at the final observation. Group 2 included 8 patients who had a progressive deterioration in renal function leading to end stage renal disease or chronic dialysis, or who died. We compared the clinical and histological features at renal biopsy and the outcome following steroid therapy between the two groups. Group 1 patients had significantly lower levels of serum creatinine and UN, and higher values for creatinine clearance (Ccr) than Group 2 patients(1.9 +/- 0.6 vs. 6.7 +/- 4.7 mg/dl, 29 +/- 7 vs. 73 +/- 39 mg/dl, 30 +/- 9 vs. 10 +/- 5 ml/min, p < 0.05, respectively). Histologically, Group 1 patients had a significantly lower percentage of crescent formation than Group 2 patients(41 +/- 6 vs. 74 +/- 4%, p < 0.05), whereas there was no significant difference in tubulo interstitial damage between the 2 groups. Moreover, in 4 patients of Group 1 where a second renal biopsy was performed two months after steroid therapy, marked attenuation in acute tubulo-interstitial changes was observed in association with a rapid improvement of renal function. These results suggest that diffuse tubulo-interstitial inflammatory changes despite a relatively low frequency of cellular crescent formation may be a prognostically important histological feature showing a good response to steroid therapy.

Acute interstitial nephritis due to drugs: Review of the literature with a report of nine cases.

Acute interstitial nephritis due to drugs commonly presents as acute renal failure and may be commoner than is presently realized. Drugs implicated include not only methicillin and other penicillins but also diuretics and nonsteroidal anti-inflammatory agents. The mechanism of injury likely involves an immunologic disturbance, possibly a delayed hypersensitivity reaction. Differential diagnosis from other causes of acute renal failure may be difficult, but coincident evidence of an acute allergic reaction may help, as may the detection of eosinophils in the urine or avid uptake of 67Ga by the kidneys. Definitive diagnosis may require renal biopsy, which will reveal normal glomeruli and a patchy but usually heavy interstitial infiltrate with lymphocytes, plasma cells, and eosinophils. Diagnosis of acute interstitial nephritis is important, because withdrawal of the offending agent will usually result in rapid improvement in renal function, and steroid therapy may reduce residual chronic renal damage.