Persistent CD-19 depletion by rituximab is cost-effective in maintaining remission in calcineurin-inhibitor dependent podocytopathy.

AIM: A significant proportion of patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are either steroid dependent or steroid resistant, requiring long-term calcineurin inhibitors (CNI) use. Rituximab has more favourable safety profile. The present study was undertaken to evaluate the efficacy and safety of rituximab in CNI-dependent patients. METHODS: This was a prospective observational study conducted from July 2014 to February 2018. Steroid-dependent nephrotic syndrome or steroid-resistant nephrotic syndrome (biopsy proven MCD/FSGS), who were CNI dependent were enrolled. Mean age at enrolment was 22.77 ± 7.45 years. All patients received rituximab at a dose of 375 mg/m2 at entry in the study. CD-19 levels were monitored monthly and patients having CD-19 levels >5/µL and/or > 1% received additional low-dose (100 mg) of rituximab. RESULTS: A total of 24 patients were followed up for 12 months. At the end of 6 and 12 months, 87.5% and 79.16% of the patients achieved remission, respectively. Eight (33.33%) patients developed relapse. The mean dose of rituximab in the first year was 791 mg. The average cost of rituximab in the first year was 487.17$. Rituximab was well-tolerated, with mild infusion reactions, respiratory tract infection and oral candidiasis in 5 (20.83%), 5 (20.83%) and 1 (4.17%) patient, respectively. CONCLUSIONS: CD-19 targeted rituximab is a safe and cost-effective agent in remission maintenance in adults with CNI dependent. Over three-fourths of the patients with CNI-dependent podocytopathy maintain clinical remission with CD-19 targeted rituximab therapy.

Apolipoprotein A-1-related amyloidosis 2 case reports and review of the literature.

RATIONALE: Apolipoprotein A-1 (ApoA-1)-related amyloidosis is characterized by the deposition of ApoA-1 in various organs and can be either hereditary or nonhereditary. It is rare and easily misdiagnosed. Renal involvement is common in hereditary ApoA-1 amyloidosis, but rare in the nonhereditary form. PATIENT CONCERNS: We reported two cases with ApoA-1 amyloidosis, a 64-year-old man suffering from nephrotic syndrome and a 40-year-old man with nephrotic syndrome and splenomegaly. Renal biopsies revealed glomerular, interstitial and vascular amyloid deposits and positive phospholipase A2 receptor staining in the glomerular capillary loop in case 1, and mesangial amyloid deposits in case 2. DIAGNOSES: After immunostaining failed to determine the specific amyloid protein, proteomic analysis of amyloid deposits by mass spectrometry was performed and demonstrated the ApoA-1 origin of the amyloid. Genetic testing revealed no mutation of the APOA1 gene in case 1 but a heterozygous mutation, Trp74Arg, in case 2. Case 1 was thus diagnosed as nonhereditary ApoA-1 associated renal amyloidosis with membranous nephropathy, and case 2 as hereditary ApoA-1 amyloidosis with multiorgan injuries (kidney and spleen) and a positive family history. INTERVENTIONS: Case 1 was treated with glucocorticoid combined with cyclosporine. Case 2 was treated with calcitriol and angiotensin converting enzyme inhibitors. OUTCOMES: Two cases were followed up for 5 months and 2 years, respectively; and case 1 was found to have attenuated proteinuria while case 2 had an elevation of cholestasis indices along with renal insufficiency. LESSONS: Proteomic analysis by mass spectrometry of the amyloid deposits combined with genetic analysis can provide accurate diagnosis of ApoA-1 amyloidosis. Besides, these 2 cases expand our knowledge of ApoA-1-related renal amyloidosis.

Renal involvement in lysinuric protein intolerance: contribution of pathology to assessment of heterogeneity of renal lesions.

Lysinuric protein intolerance (LPI) is a rare autosomal recessive disease caused by mutations in the SLC7A7 gene encoding the light subunit of a cationic amino acid transporter. Symptoms mimic primary urea cycle defects but dysimmune symptoms are also described. Renal involvement in LPI was first described in the 1980s. In 2007, it appeared that it could concern as much as 75% of LPI patients and could lead to end-stage renal disease. The most common feature is proximal tubular dysfunction and nephrocalcinosis but glomerular lesions are also reported. However, very little is known regarding histological lesions associated with LPI. We gathered every kidney biopsy of LPI-proven patients in our highly specialized pediatric and adult institution. Clinical, biological, and histological information was analyzed. Five LPI patients underwent kidney biopsy in our institution between 1986 and 2015. Clinically, 4/5 presented with proximal tubular dysfunction and 3/5 with nephrotic range proteinuria. Histology showed unspecific tubulointerstitial lesions and nephrocalcinosis in 3/5 biopsies and marked peritubular capillaritis in one child. Glomerular lesions were heterogeneous: lupus-like-full house membranoproliferative glomerulonephritis (MPGN) in one child evolved towards monotypic IgG1κ MPGN sensitive to immunomodulators. One patient presented with glomerular non-AA non-AL amyloidosis. Renal biopsy is particularly relevant in LPI presenting with glomerular symptoms for which variable histological lesions can be responsible, implying specific treatment and follow-up.

[Significance of the determination of urinary excretion of kidney injury molecule-1 (KIM-1) in the assessment of the activity and prognosis of chronic glomerulonephritis].

AIM: To estimate the urinary excretion of KIM-1 in groups of patients with varying clinical activity of chronic glomerulonephritis (CGN) and to determine the possibility of using the urinary KIM-1 concentration as a criterion for predicting the course of CGN. SUBJECTS AND METHODS: A total of 47 patients with CGN were examined. Group 1 included 10 patients with nephrotic syndrome (NS) and decreased glomerular filtration rate (GFR); Group 2 consisted of 16 patients with NS and normal GFR; Group 3 comprised 10 patients with partial remission of NS; Group 4 included 11 patients with CGN, hematuria, moderate proteinuria, and normal GFR. A control group consisted of 9 healthy individuals. In the examined groups, urinary KIM-1 concentrations were estimated using an indirect immunoassay. RESULTS: The urinary KIM-1 excretion in the patients with CGN was higher than that in the healthy individuals (p <0.0001), at the same time, in the average the KIM-1 excretion was statistically significantly higher in the patients with proteinuria than in those with hematuria (p=0.01). The highest levels were registered in Group 1; Group 2 was intermediate in the level of KIM-1 excretion and the difference between Groups 3 and 4 proved to be statistically insignificant. The lowest levels were noted in Group 4 and in the controls; the differences between the groups were statistically insignificant. In the patients with CGN, the level of KIM-1 excretion was established to correlate with all indicators of NS severity. The value of the determination of KIM-1 as a risk factor of persistent/refractory NS was estimated. The results of constructing the ROC-curve indicate that KIM-1 levels higher than 2.34 ng/ml could predict NS persistence in CGN patients with a high sensitivity and specificity. CONCLUSION: Urinary KIM-1 levels may be used to estimate the activity of CGN with NS and to evaluate the efficiency of treatment. The results of the study substantiate the search for ways of pharmacological blockade of KIM-1 production in the kidney in order to optimize the methods that impact on the pathogenesis of CGN progression.

Membranous nephropathy in the older adult: epidemiology, diagnosis and management.

Membranous nephropathy is the most important cause of the nephrotic syndrome in elderly patients (aged >65 years). The clinical presentation is similar in older and younger patients, although elderly patients more often present with renal failure. Notably, glomerular filtration rate (GFR) is usually lower in the elderly due to the physiological decline in GFR after the age of 30 years. Secondary causes, especially malignancies, are more common in older patients with membranous nephropathy. Therefore, elderly patients should undergo a thorough examination to exclude a secondary cause. The prognosis of elderly patients with idiopathic membranous nephropathy is not very different from that of younger patients. All elderly patients should receive symptomatic treatment aimed at reducing hypertension, oedema, proteinuria and hyperlipidaemia. It is recommended that elderly patients with a low serum albumin (<2 g/dL) receive prophylactic anticoagulation because of a high risk for thrombosis. Immunosuppressive therapy should be reserved for elderly patients at high risk of progression to end-stage renal disease because the elderly are particularly prone to the adverse effects and infectious complications of immunosuppressive therapy. High-risk elderly patients are characterised by renal insufficiency (GFR <45 mL/min/1.73m(2)), an increase in serum creatinine of >25% or a severe persistent nephrotic syndrome not responding to symptomatic treatment. In addition, elderly patients with a relatively normal GFR (>or=45 mL/min/1.73m(2)) and high urinary excretion of beta(2)-microglobulin and IgG are also at increased risk of developing end-stage renal disease; however, the deterioration in renal function is usually a slow process. Therefore, such patients benefit from immunosuppressive therapy only if their life expectancy is good. If immunosuppressive therapy is started, first-line treatment consists of prednisone and cyclophosphamide. If cyclophosphamide is contraindicated or fails to induce a remission, ciclosporin could be used. Treatment with ciclosporin should be limited to patients with a relatively normal renal function (GFR >60 mL/min/1.73m(2)) in view of its nephrotoxicity in patients with renal dysfunction.

Common causes of admission in diabetics.

OBJECTIVE: To report on the causes of admissions of diabetic patients to the medical unit of King Abdulaziz University Hospital, mortality and risk factors, associated with high mortality, and to find out possible ways to reduce admissions, cost and mortality. METHODS: Retrospective analysis of diabetic admissions to the medical unit of King Abdulaziz University Hospital between January 1996 to September 1999. Patients age, sex, body mass index, type and duration of diabetes mellitus, mode of treatment, degree of blood glucose control, presence of hypertension, hyperlipidemia, and smoking were recorded as well as the causes of admissions and mortality. RESULTS: A total of 5917 patients were admitted, 17% of them were diabetics. Admissions for blood glucose control and for macrovascular complications were found in 21% and 38%. Mortality rate was 13%. Hypertension, hyperlipidemia, smoking, obesity, infection, poor glycemic control, long duration of diabetes mellitus and long hospital stay were risk factors associated with high mortality. CONCLUSION: Macrovascular complications and uncontrolled blood glucose were the most common causes of admissions. Control of hypertension, hyperlipidemia, cessation of smoking and weight reduction will not only decrease the risk of macrovascular complications, but also in addition to patient's education for tight blood glucose control, will decrease the rate, cost and mortality of diabetic admissions.

[Renal complications associated with human acquired immunodeficiency virus infection in a population of hospital patients at the Hospital and University National Center in Cotonou]. / Complications rénales associées à l'infection par le virus de l'immunodéficience acquise humaine dans une population hospitalisée au CNHU de Cotonou.

We studied 92 HIV-positive patients retrospectively between January 1994 and December 1996 and prospectively from January to July 1997. We determined serum creatinine and 24-hour proteinuria. The median age of the patients was 22 (+/- 4) years and most patients were aged between 25 and 45 years. The sex ratio was 2.17 and most patients were infected with HIV-1 (67.39%). Renal failure occurred in 27.16% of cases, due to changes in blood pressure and infectious diseases. Three patients had a nephrotic syndrome caused by HIV. Thirty-eight cases of lung infection, ten of urinary infection, twelve infections of the digestive system and fifteen cases of skin infection were recorded. The median duration of stay in hospital was 23 (+/- 8) days and the median cost of hospitalization was 147,450 F CFA (+/- 31,057). The treatment given was purely symptomatic and three patients died during the study. One patient suffered chronic renal failure and is now undergoing hemodialysis. Preventive treatment would be of great value.

[Assessment of the clinical course of chronic glomerulonephritis]. / Otsenka techeniia khronicheskogo glomerulonefrita.

Clinical course of chronic glomerulonephritis (CG) with recognition of 4 types by frequency of exacerbations was investigated in 592 patients with morphologically verified diagnosis observed for a long time. The disease ran a stable course. Contrary to patients with mesangioproliferative CG who had rare or moderate-frequency exacerbations, patients with membranoproliferative disease had exacerbations annually. This suggests correlation between the form of anatomical changes and the process activity. Irrespective of CG morphological form, the survival of CG patients is closely related to the disease course. Taken into account, this fact may serve the tool of prognosis, choice of treatment intensity and duration of follow-up.

[The catamnestic assessment of the efficacy of combined pathogenetic therapy in patients with different clinico-morphological variants of chronic glomerulonephritis]. / Katamnesticheskaia otsenka éffektivnosti kompleksnoi patogeneticheskoi terapii bol'nykh s razlichnymi kliniko-morfologicheskimi variantami khronicheskogo glomerulonefrita.

In 70 patients with functionally compensated chronic glomerulonephritis (CGN), the disease outcomes were elucidated after the use of the 4-component therapy (a cytostatic, an anticoagulant, an antiaggregation agent and prednisone). The therapy appeared much more effective in the nephrotic types of CGN than in the active nephritic types. Remission was only attained in a subgroup of patients with the active types: with an early stage of the maximally active type of mesangiocapillary CGN. In the nephrotic type CGN, the therapy was effective in short-phase disease and ineffective in long persistence of that syndrome. In the nephrotic types, mesangioproliferative CGN as well as the short-phase nephrotic syndrome irrespective of the morphological type turned out predictors of a favourable outcome following the treatment. No effect can be predicted in focal segmental hyalinosis/sclerosis accompanied by arterial hypertension and the protracted nephrotic syndrome.