Karyomegalic Interstitial Nephritis-A Rare Cause Of Chronic Tubulointerstitial Nephritis

Karyomegalic Interstitial Nephritis (KIN) is a rare disease, which usually presents with slowly progressive chronic kidney disease, eventually leading to end stage renal disease in early adulthood. Histological findings consist of enlarged and hyperchromatic nuclei in scattered tubular epithelial cells throughout the nephron accompanied by interstitial fibrosis around atrophic tubules.

P0141KIDNEY BIOPSY INDICATIONS AND OUTCOMES: SEVEN YEARS EXPERIENCE OF A SINGLE CENTRE IN SRI LANKA

Background and Aims Histopathological analysis of renal biopsy is the cornerstone of diagnosis in renal disease and guides treatment and prognosis. The prevalence of various renal diseases varies according to the geographical area, socioeconomic condition, race, age, demography and indication of renal biopsy. Method A retrospective study of all native and transplant kidney biopsies performed at the renal unit of Sri Jayewardenepura General Hospital, Sri Lanka, between 1st October 2012 and 30th September 2019. Samples were processed for light microscopy in all cases, with immunofluorescence in most cases. Results 771 biopsies were analyzed. Majority of biopsies 514 (67%) were male patients. Most biopsies (n= 345, 45%) were in 40 – 59yr age group, followed by 267 (35%) 20–39yr, 117 (15%) 60–69yr, 12 (1%) >70yrs, 30 (4%) 12–19yr age groups. Maximum age was 84 years. In 35 cases, tissue were inadequate. 547 (71%) were native biopsies and 224 (29%) were graft biopsies. Among transplants, majority was for an indication (n=146, 66%) followed by time-zeroes (n=59, 26%) and protocols (n=19, 9%). Rising creatinine (81%) was the strongest reason for transplant biopsies, next proteinuria (10%) and delayed graft function (7%). Time zeroes: majority were normal, few ATN, 1 chronic tubulointerstitial nephritis, and 1 hypertensive glomerulosclerosis. Grafts revealed, acute antibody-mediated rejection 41 (18%) with acute cell-mediated rejection 27 (12%), (total rejections n=68, 30%) followed by normal histology 48 (21%), acute tubular necrosis 43 (19%), chronic allograft nephropathy 23 (10%), BKV nephropathy 5 (2%), and 18% other etiologies: CNI-toxicity (n=4), hypertensive glomerulosclerosis (n=3), diabetic nephropathy (n=2), thrombotic microangiopathy (n=2), FSGS (n=2), MPGN (n=1), vasculitis (n=2), PTLD (n=1), cast nephropathy (n=1), and granulomatous interstitial nephritis (n=1). The most common indication for native biopsy was nephrotic syndrome 209 (38%), followed by non-proteinuric CKD 105 (19%), unexplained renal failure 77 (14%), sub-nephrotic proteinuria 102 (18%), nephritic syndrome 54 (9%). Primary glomerulonephritis (GN) was the commonest 291 (53%). Commonest lesion amidst primary GN was IgA nephropathy 90 (16%), followed by FSGS 63 (12%), CGN 27 (4%), minimal change 36 (6%), MPGN 32 (5%), membranous 6 (1%), DPGN 22 (4%), mesangiocapillary GN 3 (0.5%) and post-streptococcal GN 11 (2%). In the secondary forms of GN, SLE was the commonest 39 (7%), next diabetic nephropathy 29 (5%), amyloidosis 2 (0.3%). Chronic tubulointerstitial nephritis 92 (16%) was the second common, with 42 (7%) CINAC – chronic interstitial nephritis in agricultural communities. Other etiologies: acute tubulointerstitial nephritis 14 (2.5%), hypertensive glomerulosclerosis 12 (2%), thrombotic microangiopathy 6 (1%), ischemic nephropathy 9 (1%), end stage disease 6 (1%), inconclusive 13 (2%). 5 cast nephropathy due to multiple myeloma, 1 monoclonal deposition disease due to lambda chain deposition, 1 sarcoidosis, 1 cholesterol embolism. Conclusion Female: male ratio 1:2 with commonest age group being 40 – 59yrs. Strongest indication for transplant biopsy was rising creatinine. Acute rejection was the most frequent finding in grafts, with normal histology being the next, probably due to high number of time zeroes and protocols performed in our centre. Biopsy proven BKV nephropathy was 2% (n=5). Nephrotic range proteinuria was the commonest native biopsy indication, with non-proteinuric CKD being the second. Primary GN was the commonest finding with IgA nephropathy scoring the highest. This does not coincide with global data, which shows FSGS to be the leading cause. The second common histology was FSGS, and primary CTIN was third. The prevalence of biopsy-proven GN varies due to a wide array of factors and different studies have shown different leading patterns.

Renal Manifestations of Common Variable Immunodeficiency

BackgroundCommon variable immunodeficiency (CVID) is one of the most common primary immunodeficiency syndromes, affecting one in 25,000–50,000 people. Renal insufficiency occurs in approximately 2% of patients with CVID. To date, there are no case series of renal biopsies from patients with CVID, making it difficult to determine whether individual cases of renal disease in CVID represent sporadic events or are related to the underlying pathophysiology. We performed a retrospective analysis of renal biopsy specimens in our database from patients with a clinical history of CVID (n=22 patients, 27 biopsies).MethodsLight, immunofluorescence, and electron microscopy were reviewed. IgG subclasses, PLA2R immunohistochemistry, and THSD7A, EXT1, and NELL1 immunofluorescence were performed on all membranous glomerulopathy cases. CD3, CD4, CD8, and CD20 immunohistochemistry was performed on cases of tubulointerstitial nephritis.ResultsAKI and proteinuria were the leading indications for renal biopsy in patients with CVID. Immune-complex glomerulopathy was present in 12 of 22 (54.5%) cases, including nine cases with membranous glomerulopathy, one case with a C3 glomerulopathy, and one case with membranoproliferative GN with IgG3κ deposits. All membranous glomerulopathy cases were PLA2R, THSD7A, EXT1, and NELL1 negative. The second most common renal biopsy diagnosis was chronic tubulointerstitial nephritis, affecting 33% of patients. All tubulointerstitial nephritis cases showed tubulitis and a lymphocytic infiltrate with >90% CD3+ T cells. Other renal biopsy diagnoses within our cohort included acute tubular injury (n=1), amyloid light-chain amyloidosis (n=1), diabetic glomerulosclerosis (n=1), thin basement membranes (n=1), pauci-immune GN (n=1), and arterionephrosclerosis (n=1).ConclusionsMembranous glomerulopathy and tubulointerstitial nephritis were the predominant pathologic findings in patients with CVID. Membranous glomerulopathy cases in patients with CVID were IgG1 subclass dominant and showed mesangial immune deposits. Four of the membranous glomerulopathy cases had associated proliferation, with mesangial and/or endocapillary hypercellularity, with or without crescent formation. CVID should be considered as a potential cause when membranous glomerulopathy or chronic tubulointerstitial nephritis is seen in a young patient with a history of recurrent infections.

Chronic tubulointerstitial nephritis

Chronic tubulointerstitial nephritis is usually asymptomatic, presenting with slowly progressive renal impairment. Urinalysis may be normal or show low-grade proteinuria (<1.5 g/day) and/or pyuria. Diagnosis depends on renal biopsy, which reveals variable cellular infiltration of the interstitium, tubular atrophy, and fibrosis. There are many causes including sarcoidosis, drugs (prescribed and nonprescribed), irradiation, toxins, and metabolic disorders. Analgesic nephropathy—characterized by renal papillary necrosis and chronic interstitial nephritis and caused by the prolonged and excessive consumption of combinations of analgesics, mostly including phenacetin. Nonsteroidal anti-inflammatory drugs—the most frequent cause of permanent renal insufficiency after acute interstitial nephritis. Aristolochic acid nephropathy—(1) Chinese herb nephropathy—caused in most cases (but perhaps not all) by aristolochic acid, and is associated with a high incidence of urothelial malignancy. (2) Balkan endemic nephropathy—a chronic, familial, noninflammatory tubulointerstitial disease of the kidneys that is associated with a high frequency of urothelial atypia, occasionally culminating in tumours of the renal pelvis and urethra. 5-Aminosalicylic acid—used in the treatment of chronic inflammatory bowel disease and causes clinical nephrotoxicity in approximately 1 in 4000 patients/year. Chronic interstitial nephritis in agricultural communities (CINAC) —nonproteinuric chronic kidney disease that presents in young, agricultural workers in Central America and Sri Lanka in the absence of any clear aetiology. Lithium—the most common renal side effect is to cause nephrogenic diabetes insipidus. Radiation nephropathy—preventive shielding of the kidneys in patients receiving radiation therapy generally prevents radiation nephropathy, but total body irradiation preceding bone marrow transplantation leads 20% to develop chronic renal failure in the long term. Nephropathies induced by toxins (including lead and cadmium) or by metabolic disorders (chronic hypokalaemia and chronic urate nephropathy).