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Fulltext Primary focal segmental GlomerulosSclerosis and minimal change disease as one spectrum of disease

Fah, Then Ru, Jun, Tan Yi, Lim, Christopher Thiam Seong

Malaysian Journal of Medicine and Health Sciences, 2018;14(3):64-66.
MyJurnal

Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are common causes of nephrotic syndrome. These two conditions are similar in their presentations but differentiated via their histopathological features and responsiveness to corticosteroids. There are ongoing debates whether MCD and FSGS are at the same spectrum of disease rather than separate entities. FSGS has been postulated to be the severe end of the spectrum of MCD. We have reported a case that has primary FSGS after years of poorly controlled MCD, which supports both conditions are the same spectrum of disease.

Matched MeSH terms: Glomerulosclerosis, Focal Segmental
Fulltext Contribution of Coiled-Coil Assembly to Ca2+/Calmodulin-Dependent Inactivation of TRPC6 Channel and its Impacts on FSGS-Associated Phenotypes

Polat OK, Uno M, Maruyama T, Tran HN, Imamura K, Wong CF, et al.

J Am Soc Nephrol, 2019 09;30(9):1587-1603.
PMID: 31266820 DOI: 10.1681/ASN.2018070756

BACKGROUND: TRPC6 is a nonselective cation channel, and mutations of this gene are associated with FSGS. These mutations are associated with TRPC6 current amplitude amplification and/or delay of the channel inactivation (gain-of-function phenotype). However, the mechanism of the gain-of-function in TRPC6 activity has not yet been clearly solved.
METHODS: We performed electrophysiologic, biochemical, and biophysical experiments to elucidate the molecular mechanism underlying calmodulin (CaM)-mediated Ca2+-dependent inactivation (CDI) of TRPC6. To address the pathophysiologic contribution of CDI, we assessed the actin filament organization in cultured mouse podocytes.
RESULTS: Both lobes of CaM helped induce CDI. Moreover, CaM binding to the TRPC6 CaM-binding domain (CBD) was Ca2+-dependent and exhibited a 1:2 (CaM/CBD) stoichiometry. The TRPC6 coiled-coil assembly, which brought two CBDs into adequate proximity, was essential for CDI. Deletion of the coiled-coil slowed CDI of TRPC6, indicating that the coiled-coil assembly configures both lobes of CaM binding on two CBDs to induce normal CDI. The FSGS-associated TRPC6 mutations within the coiled-coil severely delayed CDI and often increased TRPC6 current amplitudes. In cultured mouse podocytes, FSGS-associated channels and CaM mutations led to sustained Ca2+ elevations and a disorganized cytoskeleton.
CONCLUSIONS: The gain-of-function mechanism found in FSGS-causing mutations in TRPC6 can be explained by impairments of the CDI, caused by disruptions of TRPC's coiled-coil assembly which is essential for CaM binding. The resulting excess Ca2+ may contribute to structural damage in the podocytes.

Matched MeSH terms: Glomerulosclerosis, Focal Segmental/genetics*; Glomerulosclerosis, Focal Segmental/metabolism
Intravenous Rituximab in Severe Refractory Primary Focal Segmental Glomerulosclerosis

Wee Leng G, Mustafar R, Kamaruzaman L, Mohd R, Cader RA, Wei Yen K, et al.

Acta Med Indones, 2018 Jul;50(3):237-243.
PMID: 30333274

Managing primary or even secondary glomerulonephritis remains a challenge to many nephrologists. In primary focal segmental glomerulosclerosis (FSGS) with heavy proteinuria, renin aldosterone system blockade and high dose of oral prednisolone is the mainstay of treatment. Other immunosuppressive medications like Cyclophosphamide, Cyclosporine A and Mycophenolate Mofetil (MMF) are warranted if a complete remission is not achieved. We illustrate a case of 21 year old gentleman with primary FSGS that was difficult to achieve remission despite on high dose steroid and oral Cyclophosphamide. He was also not responsive to a combination of MMF and Cyclosporine A (CSA) and even throughout the therapy he developed significant steroid and CSA toxicity. He presented to our center with severe nephrotic syndrome and acute kidney injury requiring acute haemodialysis. Despite re-challenged him again on high dose prednisolone, total of 2.4g of intravenous Cyclophosphamide, and MMF, he failed to achieve remission. He was subsequently given intravenous Rituximab 500mg/weekly for 4 doses and able to attained remission for 1 year. He relapsed again and a second course of Rituximab 500mg/weekly for 6 doses were given to attain remission. This case demonstrates the difficulty in managing refractory steroid dependent FSGS and we found that Rituximab is proven beneficial in this case to induce remission.

Matched MeSH terms: Glomerulosclerosis, Focal Segmental/drug therapy*; Glomerulosclerosis, Focal Segmental/pathology
Clinical predictors of non-diabetic renal disease and role of renal biopsy in diabetic patients with renal involvement: a single centre review

Chong YB, Keng TC, Tan LP, Ng KP, Kong WY, Wong CM, et al.

Ren Fail, 2012;34(3):323-8.
PMID: 22250665 DOI: 10.3109/0886022X.2011.647302

BACKGROUND:
Type 2 diabetes mellitus (T2DM) is reportedly the leading cause of end-stage renal disease (ESRD) worldwide. However, non-diabetic renal diseases (NDRD) are not uncommon among T2DM patients with renal involvement. Our study aimed to examine the prevalence of NDRD in T2DM and clinical markers for diabetic nephropathy (DN) and NDRD and to determine the role of renal biopsy in T2DM patients and its impact on clinical practice.

METHODS:
We conducted a retrospective analysis of T2DM patients in whom renal biopsies were performed from January 2004 to March 2008 (n = 110).

RESULTS:
Biopsy results were divided into three groups: group I/pure DN (62.7%), group II/isolated NDRD (18.2%), and group III/mixed lesions (19.1%). The causes of NDRD in decreasing order of frequency were acute interstitial nephritis, glomerulonephritides, hypertensive renal disease, and acute tubular necrosis. Significant clinical markers for DN are presence of diabetic retinopathy and longer duration of diabetes. For NDRD, useful clinical markers include the presence of acute renal failure and microscopic hematuria. In the DN subgroup, Indians had significantly shorter duration of diabetes on biopsy compared with Malays and Chinese.

CONCLUSIONS:
NDRD is prevalent in T2DM patients, and given its potentially treatable nature, renal biopsy should be considered in T2DM patients with nephropathy, especially in those with atypical features.

Matched MeSH terms: Glomerulosclerosis, Focal Segmental/etiology; Glomerulosclerosis, Focal Segmental/epidemiology; Glomerulosclerosis, Focal Segmental/pathology*
Renal biopsies in children in HUSM, Kelantan: indications, results and complications

Van Rostenberghe H, Nik Abidin NZ, Samarendra S

Malaysian Journal of Child Health, 1997;9(2):166-169.
MyJurnal

During a period of three years (February 1995 --January 1998), 30 biopsies were performed for patients within the paediatric age group in Hospital Universiti Sains Malaysia (HUSM). The majority of these patients (19 cases) had steroid-resistant Nephrotic Syndrome. Other indications were lupus erythematosus (5 cases), acute or chronic glomerulonephritis (5 cases) and infantile nephrotic syndrome (1 case). The biopsy of the 19 cases of steroid-resistant nephrotic syndrome gave the following findings: 10 showed minimal- change nephrotic syndrome, 4 focal segmental glomerulosclerosis, 3 mesangial proliferative glomerulonephritis and one diffuse sclerosing glomerulonephritis while there was insufficient glomeruli for a conclusive diagnosis in one case. The 5 patients with acute/chronic glomerulonephritis showed diffused sclerosing glomerulonephritis. The other 5 patients with lupus nephritis showed mesangial proliferative glomerulonephritis (2) and severe proliferative glomerulonephritis (3). The 5-month-old child with infantile nephrotic syndrome showed mesangial proliferative glomerulonephritis. There were no severe complications noted during or immediately after the procedure. There were 3 cases of gross haematuria, one lasting less than 24 hours and the other two less than

Matched MeSH terms: Glomerulosclerosis, Focal Segmental
The changing pattern of primary glomerulonephritis in Singapore and other countries over the past 3 decades

Woo KT, Chan CM, Mooi CY, -L-Choong H, Tan HK, Foo M, et al.

Clin. Nephrol., 2010 Nov;74(5):372-83.
PMID: 20979946

This review of 2,586 renal biopsies over the past 3 decades in Singapore documents the changing pattern of glomerulonephritis (GN) from that of a third world country to that of a developed nation. In the 1st decade, mesangial proliferative glomerulonephritis was the most common form of primary GN, just as it was in the surrounding Asian countries. In the 2nd decade, the prevalence of mesangial proliferative GN decreased with a rise in membranous, GN which is also seen in China and Thailand. In the 3rd decade, there was a dramatic increase in focal sclerosing glomerulosclerosis. This increase reflects aging and obesity in keeping with more developed countries like Australia, India, Thailand and the United States of America. IgA nephritis remains the most common GN. Apart from the geographical influence, other socioeconomic factors play a significant role in the evolution of the renal biopsy pattern. Mesangial proliferative GN remains prevalent in many Asian countries, but in Singapore the prevalence is decreasing just as it is in Japan, Korea and Malaysia. Worldwide, the prevalence of focal sclerosing glomerulosclerosis continues to increase in many countries.

Matched MeSH terms: Glomerulosclerosis, Focal Segmental/epidemiology; Glomerulosclerosis, Focal Segmental/pathology
Pattern of biopsy-proven renal disease in Sabah: A retrospective cross-sectional study over 3.5 years

Lee AV, Pang HC, Linus Lojikip S, Wong KW, Goh KW, Chan FS

Med J Malaysia, 2020 03;75(2):152-157.
PMID: 32281597

OBJECTIVES: To explore the epidemiological and histopathological patterns of glomerular diseases in Sabah.
METHODS: A state-wide cross-sectional study was conducted. There were 336 native renal biopsies in 296 eligible patients from 1st January 2013 to 30th June 2016. All patients aged ≥12 years with sufficient sampling (≥8 glomeruli) for histopathological assessment were included. Graft kidney biopsies, protocol-based biopsies and patients with uncertain demographics were excluded. Demographics of patients, clinical data, laboratory parameters prior to biopsy, and histology findings of renal biopsies were collected from local unit database and recorded into a standardised data collection form. Descriptive statistical analyses were employed and factors associated with Lupus nephritis (LN) were explored using logistic regression.
RESULTS: The mean age during biopsy was 34.53 years (Standard Deviation 0.759). Primary glomerulonephritis (PGN) accounted for 42.6% (126) of all native renal biopsies. The commonest cause of PGN was minimal change disease (38.9%, 49) followed by focal segmental glomerulosclerosis (33.3%, 42) and IgA nephropathy (14.3%, 18). LN is the leading cause for secondary glomerulonephritis (SGN) (87.2%, 136). Younger age (Odds Ratio, OR 0.978; 95% Confidence Interval, 95%CI 0.960, 0.996); female gender (OR 17.53; p<0.001); significant proteinuria (OR 132.0; p<0.001); creatinine level at biopsy (OR 11.26; p=0.004); positive antinuclear antibody (ANA) (OR 46.7; p<0.001); and ANA patterns (OR 8.038; p=0.018) were significant in predicting the odds of having LN.
CONCLUSION: This is the first epidemiology study of glomerular diseases in Sabah. The predominance of LN suggests lower threshold for renal biopsy in patients with suspected glomerular disorders. We have identified significant predictors for early detection and treatment of LN.

Matched MeSH terms: Glomerulosclerosis, Focal Segmental