Causes of Granulomatous Inflammation in Native and Allograft Kidneys: Case Series from A Single Center and A Review of the Literature.

OBJECTIVE: Granulomatous interstitial nephritis is a rare finding, and etiology differs by geography. We aimed to investigate the distribution of causes of granuloma/granulomata in the kidney and renal survival of these patients in a tertiary care hospital in Western Turkey. MATERIAL AND METHOD: Medical records of adults who underwent a kidney biopsy procedure in our institution between January 2000 and June 2019 were reviewed. Pathology reports were searched for biopsies where a granuloma was identified. RESULTS: Nineteen of 1121 (1.7%) kidney biopsies included granuloma, 17 in native kidneys, and 2 in transplants. The majority of indications for native kidney biopsy was a rise in serum creatinine. Etiologies of granuloma included the following: pauci-immune vasculitis (n=11, 64.7%), tuberculosis (n=2, 11.8%), drug-induced (n=2, 11.8%), tubulointerstitial nephritis/uveitis (TINU) syndrome (n=1, 5.9%), and systemic-lupus erythematosus (n=1, 5.9%). Despite treatment, 6 of 11 (54.5%) patients with vasculitis developed end-stage kidney disease (ESKD) during the median follow-up of 16 months. Both of the patients with tuberculosis, and the patient with TINU syndrome developed ESKD months after the kidney biopsy, despite appropriate therapies. The only case with drug-induced granuloma and both cases with allograft kidney granuloma responded well to glucocorticoids, achieving a complete renal recovery. CONCLUSION: The majority of our series had granuloma in the kidney secondary to vasculitis and renal outcomes appear considerably unfavorable despite treatment, probably related to the primary diagnosis. Multicenter studies are needed to better determine the etiology and outcome of each granuloma etiology at different geographic locations.

UNUSUAL PRESENTATIONS OF LMNA-ASSOCIATED LIPODYSTROPHY WITH COMPLEX PHENOTYPES AND GENERALIZED FAT LOSS: WHEN THE GENETIC DIAGNOSIS UNCOVERS NOVEL FEATURES.

OBJECTIVE: Lipodystrophy represents a group of rare diseases characterized by loss of body fat. While patients with generalized lipodystrophy exhibit near-total lack of fat, partial lipodystrophy is associated with selective fat loss affecting certain parts of the body. Although classical familial partial lipodystrophy (FPLD) is a well-described entity, recent reports indicate phenotypic heterogeneity among carriers of LMNA pathogenic variants. METHODS: We have encountered 2 unique cases with complex phenotypes, generalized fat loss, and very low leptin levels that made the distinction between generalized versus partial lipodystrophy quite challenging. RESULTS: We present a 61-year-old female with generalized fat loss, harboring the heterozygous pathogenic variant p.R541P (c.1622G>C) on the LMNA gene. The discovery of the pathogenic variant led to correct clinical diagnosis of her muscle disease, identification of significant heart disease, and a recommendation for the implantation of a defibrillator. She was able to start metreleptin based on her generalized fat loss pattern and demonstration of the genetic variant. Secondly, we report a 40-year-old Turkish female with generalized fat loss associated with a novel heterozygous LMNA pathogenic variant p.K486E (c.1456A>G), who developed systemic B cell follicular lymphoma. CONCLUSION: Clinicians need to recognize that the presence of an LMNA variant does not universally lead to FPLD type 2, but may lead to a phenotype that is more complex and may resemble more closely generalized lipo-dystrophy. Additionally, providers should recognize the multisystem features of laminopathies and should screen for these features in affected patients, especially if the variant is not at the known hotspot for FPLD type 2.