Cyclosporine A Treatment of Proteinuria in a New Case of MAFB-Associated Glomerulopathy without Extrarenal Involvement: A Case Report

The <i>MAFB</i> gene encodes an important basic leucine zipper transcription factor that functions in glomerular podocytes, macrophages, and osteoclasts. Recently, <i>MAFB</i> was identified as the gene that was responsible for causing nephropathy with focal segmental glomerulosclerosis (FSGS) with multicentric carpotarsal osteolysis (MCTO) or Duane retraction syndrome (DRS). Here, we describe a patient with nephropathy associated with FSGS who exhibited a novel stop-gain variant in the <i>MAFB</i> gene (NM_005461:c.590C&#x3e;A (p.Ser197Ter)). The patient’s father exhibited proteinuria with FSGS with possible DRS, whereas the patient exhibited nephropathy with FSGS and nearly normal eye movement and hearing function, as well as intact bone structure in the extremities. Conventional oral steroids or immunosuppressive drugs have not demonstrated effectiveness for patients with nephropathy who exhibit pathogenic variants in <i>MAFB</i>, except for a patient with nephropathy with FSGS and MCTO who experienced attenuated proteinuria within the subnephrotic range in response to cyclosporine A (CyA) treatment for at least 4 years. Thus, we attempted administration of CyA in our patient. Unexpectedly, the patient demonstrated good and rapid responses to CyA, including a partial reduction in proteinuria from approximately 2.0 g/g Cr to proteinuria within the subnephrotic range (0.27 g/g Cr) after 13 months of observation. Our findings suggest that CyA may be a suitable treatment option for patients with nephropathy with FSGS who exhibit pathogenic <i>MAFB</i> variants.

Horseshoe Kidney in Conjunction With Autosomal Dominant Polycystic Kidney Disease: A Case Report

Horseshoe kidney in the presence of autosomal dominant polycystic kidney disease is a rare occurrence of two relatively common and unrelated renal findings. Visualization of multiple, bilateral cysts along with fusion of the kidneys by a midline isthmus can usually isolate these diagnoses. Accurate sonographic evaluation is essential in determining the degree of disease progression and possible complications associated with these diseases. Sonography is also useful in identifying extrarenal involvement and eliminating differential diagnoses.

Light chain deposition disease involving kidney and liver in a patient with IgD myeloma

Background IgD multiple myeloma (MM) is a rare subtype of MM and light chain deposition disease (LCDD) outside the kidney is also a rare and has scarcely been reported. We report herein the details of the first reported case of LCDD involving the kidney and liver co-occurring with IgD myeloma. Case presentation A 66-year-old female with IgD MM presented with rapidly progressive acute renal failure, ascites and pleural effusion. Immunofluorescent study of revealed the characteristic linear deposition of Igκ light chain along the glomerular and tubular basement membrane in kidney. Electron microscopy showed the powdery electron-dense deposits along the tubular and glomerular basement membrane consistent with the diagnosis of LCDD. Laser microdissection followed by mass spectrometry identified only Igκ light chain with more than 95% probability confirm the diagnosis of κ-LCDD but not heavy/light chain deposition disease. Liver biopsy with immunofluorescence study revealed the linear deposition of Igκ chain along the perisinusoidal space indicating the hepatic involvement of κ-LCDD. The patient was successfully treated with combination therapy with bortezomib, cyclophosphamide, dexamethasone, and daratumumab. Conclusions This report emphasizes that prompt biopsy of affected organs and initiation of clone directed therapy led to the correct diagnosis and favorable outcome in patient with LCDD who has extrarenal involvement.

Idiopathic granulomatous interstitial nephritis and isolated renal sarcoidosis: Two diagnoses of exclusion

Granulomatous interstitial nephritis is a rare finding in renal biopsy caused by drugs, infections, and inflammatory or autoimmune diseases. Idiopathic cases account for 18% of granulomatous interstitial nephritis in native kidneys. Sarcoidosis and drugs are the most common causes of granulomatous interstitial nephritis in Western countries, while in India tuberculosis prevails. Few cases of renal sarcoidosis without extrarenal involvement, that is, isolated renal sarcoidosis, have been reported. The diagnostic criteria of isolated renal sarcoidosis remain, however, unclear. Extrarenal sarcoidosis and other etiologies of granulomatous interstitial nephritis, in particular drug-related, have to be excluded. Some of these patients may develop extrarenal manifestations during follow-up. Changes in calcium and vitamin D metabolism are frequently observed in renal sarcoidosis and support its diagnosis. While non-necrotizing granulomas are a feature of sarcoidosis and drug-induced granulomatous interstitial nephritis, they also prevail in tuberculosis-associated granulomatous interstitial nephritis. Granulomatous interstitial nephritis caused by sarcoidosis and drugs usually responds to steroid therapy. A poor response to steroids may indicate an infectious etiology such as tuberculosis and should lead to a review of the initial diagnosis. This article gives an overview of the various etiologies of granulomatous interstitial nephritis, their frequency and histopathological characteristics, as well as potential biomarkers associated with renal sarcoidosis.

X-Linked Alport Syndrome in Women: Genotype and Clinical Course in 24 Cases

Objectives: X-linked Alport syndrome (XLAS) females are at risk of developing proteinuria and chronic kidney damage (CKD). The aim of this study is to evaluate the genotype-phenotype correlation in this rare population.Materials and Methods: This is a prospective, observational study of XLAS females, confirmed by a pathogenic mutation in COL4A5 and renal ultrastructural evaluation. Proteinuria, renal function and extrarenal involvement were monitored during follow-up. Patients were divided in 2 groups, according to mutations in COL4A5: missense (Group 1) and non-missense variants (Group 2).Results: Twenty-four XLAS females, aged 10.6 ± 10.4 years at clinical onset (mean follow-up: 13.1 ± 12.6 years) were recruited between 2000 and 2017 at a single center. In group 1 there were 10 patients and in group 2, 14 (mean age at the end of follow-up: 24.9 ± 13.6 and 23.2 ± 13.8 years, respectively). One patient in Group 1 and 9 in Group 2 (p = 0.013) developed proteinuria during follow-up. Mean eGFR at last follow-up was lower in Group 2 (p = 0.027), where two patients developed CKD. No differences in hearing loss were documented among the two groups. Two patients in Group 2 carried one mutation in both COL4A5 and COL4A3 (digenic inheritance) and were proteinuric. In one family, the mother presented only hematuria while the daughter was proteinuric and presented a greater inactivation of the X chromosome carrying the wild-type allele.Conclusions: The appearance of proteinuria and CKD is more frequent in patients with severe variants. Carrying digenic inheritance and skewed XCI seem to be additional risk factors for proteinuria in XLAS females.

Study of Anti-Müllerian Hormone and Its Relation to the Subsequent Probability of Pregnancy in 112 Patients With Systemic Lupus Erythematosus, Exposed or Not to Cyclophosphamide

Context: Cyclophosphamide is used for renal and major extrarenal involvement in systemic lupus erythematosus (SLE) and is associated with a risk of premature ovarian failure. There are no data available about the relation between anti-Müllerian hormone (AMH) serum levels and the probability of subsequent pregnancy in SLE patients. Objective: We analyzed AMH levels and the probability of pregnancy in SLE women exposed to cyclophosphamide. Design and Setting: We conducted a matched cohort study in referral centers for SLE. Patients: Fifty-six cyclophosphamide-exposed SLE women younger than 40 years of age and 56 control SLE women matched for age within 6 months participated in the study. Main Outcome Measures: AMH was measured in samples from the PLUS study (ClinicalTrials.gov no. NCT00413361). All patients were interviewed in May 2012 regarding their obstetric status. Results: The mean age ± SD of the 112 patients was 31.6 ± 5.8 years. The mean AMH level was low (1.21 ± 1.01 ng/mL) and was significantly lower in patients exposed to cyclophosphamide (P = .03) and in patients older than 30 years (P = .02). During a median follow-up (interval between sampling and the interview) period of 4.2 (range, 2.5–4.8) years, 38 patients sought to become pregnant, and 32 (84.2%) succeeded. In the univariate analysis, the risk of failure was associated with cumulative cyclophosphamide dose (P = .007) and older age (P = .02), but not with AMH. Conclusion: We confirmed that AMH levels are low in SLE patients and decrease significantly with age and cyclophosphamide exposure. Nonetheless, the risk of failure to conceive was low and was predicted by cyclophosphamide exposure and age, but not by AMH levels.

Tomographic aspects of xanthogranulomatous pyelonephritis and related complications

The authors present their experience involving seven patients with histopathologic diagnosis of xanthogranulomatous pyelonephritis who were submitted to preoperative computed tomography (CT). The results are the following: a) stones (86 percent of the cases), b) increase in renal volume, c) hydronephrosis, d) density measurements (from 14 to 29 HU), e) enhancement found in all cases, f) extrarenal involvement (all cases). CT has shown to be a reliable method in characterizing xanthogranulomatous xyelonephritis and extrarenal involvement.