Collapsing Focal Segmental Glomerulosclerosis Following Treatment with High-Dose Pamidronate

Abstract. Collapsing focal segmental glomerulosclerosis (FSGS) is a distinct clinicopathologic entity seen most commonly in young African American patients who present with renal insufficiency and nephrotic syndrome. The only epidemiologic factor previously linked to collapsing FSGS is HIV infection. Here clinicopathologic findings are reported for a distinctive population of seven patients, who were older, Caucasian, and HIV negative and developed collapsing FSGS during active treatment of malignancy (multiple myeloma in six patients and metastatic breast carcinoma in one). Although oncologic treatment regimens included vincristine for four patients, doxorubicin for five patients, cisplatin for two patients, and total-body irradiation for one patient, the only agent common to all patients was pamidronate (Aredia). All patients had normal renal function before the administration of pamidronate. Patients began therapy with pamidronate at or below the recommended dose of 90 mg, intravenously, monthly, which was increased to 180 mg monthly in two patients and 360 mg monthly in three patients. Patients received pamidronate for 15 to 48 mo before presentation with renal insufficiency (mean serum creatinine, 3.6 mg/dl) and full nephrotic syndrome (mean 24-h urinary protein excretion, 12.4 g/d). Pamidronate, which is a member of the class of bisphosphonates, is widely used in the treatment of hypercalcemia of malignancy and osteolytic metastases. At the recommended dose of 90 mg, intravenously, monthly, renal toxicity is infrequent; however, higher doses have produced nephrotoxicity in animal models. The temporal association between pamidronate therapy and the development of renal insufficiency, the use of escalating doses that exceed recommended levels, and the distinctive pattern of glomerular and tubular injury strongly suggest a mechanism of drug-associated podocyte and tubular toxicity. These data provide the first association of collapsing FSGS with toxicity to a therapeutic agent.

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Collapsing focal segmental glomerulosclerosis probably triggered by dengue virus infection - two case reports

Brazilian Journal of Nephrology ◽

10.1590/2175-8239-jbn-2019-0237 ◽

2020 ◽

Author(s):

Patrícia Cruz Queiroz ◽

Ana Elisa Souza Jorge ◽

Plínio Henrique Vaz Mourão ◽

Maria Goretti Moreira Guimarães Penido

Keyword(s):

Renal Function ◽

Nephrotic Syndrome ◽

Virus Infection ◽

Dengue Virus ◽

Focal Segmental Glomerulosclerosis ◽

Case Reports ◽

Kidney Injury ◽

Dengue Virus Infection ◽

Segmental Glomerulosclerosis ◽

Collapsing Fsgs

Abstract The reported cases describe the association between collapsing focal segmental glomerulosclerosis (FSGS) and acute dengue virus infection. In both cases, patients were diagnosed with dengue virus infection and had a severe kidney disease, with nephrotic syndrome and acute kidney injury. Kidney biopsy was performed and showed collapsing FSGS. The first patient, a 27-year-old man, was diagnosed with dengue virus infection and developed nephrotic syndrome after two weeks of illness. He was treated with methylprednisolone for three days and intravenous furosemide. This patient evolved well, although his renal function did not fully recover. The second patient, a 32-year-old man, was diagnosed with a milder clinical presentation of dengue virus infection. He had a past medical history of nephrotic syndrome in childhood, which might have caused its relapse. This patient was treated with intravenous furosemide and also did not fully recover renal function. These cases highlight the possible implication of dengue virus infection in the etiology of collapsing variant of FSGS. Healthcare professionals should be prepared to identify similar cases.

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Primary focal segmental glomerulosclerosis

10.1093/med/9780199592548.003.0057_update_001 ◽

2018 ◽

Author(s):

Alain Meyrier ◽

Patrick Niaudet

Keyword(s):

Focal Segmental Glomerulosclerosis ◽

Viral Infections ◽

Therapy Response ◽

High Dose ◽

African Origin ◽

Donor Kidney ◽

Progressive Loss ◽

Segmental Glomerulosclerosis ◽

Collapsing Fsgs ◽

Focal Segmental Sclerosis

Primary focal segmental glomerulosclerosis (FSGS) causes nephrotic syndrome and by definition is not caused by any of the known causes of podocyte toxicity or focal segmental sclerosis such as viral infections or toxins. A number of genetic causes of FSGS are commonly diagnosed in early childhood. Other causes of segmental scarring need to be distinguished. Genotypes in APOL1 of African origin are associated with higher incidence of FSGS and poorer responses to treatment. Cellular and collapsing FSGS are variants of FSGS in which there is overt acute podocytopathy and they have a relatively poor prognosis. A glomerular tip lesion is thought to have a slightly better prognosis than other types. Some cases of primary FSGS respond to high-dose corticosteroids, sometimes only after prolonged therapy. Response to steroids is a good prognostic sign, and without a response, progressive loss of renal function is likely. A circulating factor is implicated by the observation that proteinuria can recur in a donor kidney within hours of transplant. Plasma exchange appears to remove this factor but it is not conclusively identified.

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Treatment of childhood nephrotic syndrome.

Journal of the American Society of Nephrology ◽

10.1681/asn.v34889 ◽

1992 ◽

Vol 3 (4) ◽

pp. 889-894

Author(s):

S A Mendoza ◽

B M Tune

Keyword(s):

Nephrotic Syndrome ◽

Focal Segmental Glomerulosclerosis ◽

Alkylating Agent ◽

Controlled Trial ◽

Current Data ◽

High Dose ◽

Converting Enzyme Inhibitors ◽

Childhood Nephrotic Syndrome ◽

Segmental Glomerulosclerosis ◽

Daily Prednisone

This review examines selected aspects of the treatment of the nephrotic syndrome in children. Particular attention has been paid to two groups of nephrotic children. First, children with steroid-responsive nephrotic syndrome are discussed. Recently, a series of controlled studies have provided important information regarding the optimal duration of steroid therapy. Initial episodes of the nephrotic syndrome are best treated with "long" courses of prednisone therapy (6 wk of high-dose daily prednisone followed by 6 wk of alternate-day prednisone). In contrast, relapses do as well with "short" courses (about 2 wk of daily prednisone and 2 wk of alternate-day therapy). Some children who are steroid responsive require high doses of prednisone to remain in remission. These patients may require alkylating agent therapy. The most common cause of steroid-resistant nephrotic syndrome is focal segmental glomerulosclerosis. Over the past 10 yr, these patients have been treated with an intensive protocol involving multiple infusions of high-dose methylprednisolone and, in many cases, oral alkylating agent therapy. Current experience with this treatment is presented. The protocol appears to improve the outcome in children with focal segmental glomerulosclerosis, although it is believed that it is essential that these observations be confirmed by a controlled trial. There is also interest in the use of angiotensin-converting enzyme inhibitors and cyclosporine in the treatment of childhood nephrotic syndrome. The experience with these agents is briefly reviewed, but the current data are inadequate to indicate their role(s) in this condition.

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Primary focal segmental glomerulosclerosis

10.1093/med/9780199592548.003.0058_update_001 ◽

2018 ◽

Author(s):

Alain Meyrier ◽

Patrick Niaudet

Keyword(s):

Nephrotic Syndrome ◽

Focal Segmental Glomerulosclerosis ◽

Remission Rate ◽

Calcineurin Inhibitors ◽

Steroid Treatment ◽

High Dose ◽

Glomerular Injury ◽

Asian Patients ◽

Segmental Glomerulosclerosis ◽

Black Patients

The proportion of cases of primary focal segmental glomerulosclerosis responsive to treatment with corticosteroids is variable and depends on histological type, patient age and duration, and dose of steroid treatment, but overall complete remission rate is estimated at 20–25% in white and Asian patients, and lower in black patients. Partial response dependent on a high dose of steroids is common. Despite anxieties about nephrotoxicity, there may be justification for adding calcineurin inhibitors to control nephrotic syndrome if it is severe. Data for additional agents is not very encouraging. Plasma exchange appears to remove a circulating factor that causes proteinuria in focal segmental glomerulosclerosis, as illustrated by responses to this treatment when proteinuria recurs acutely after kidney transplantation. This is rarely pursued clinically except after transplantation, in advance of severe glomerular injury.

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Clinical manifestations of focal segmental glomerulosclerosis in Japan from the Japan Renal Biopsy Registry: age stratification and comparison with minimal change disease

Scientific Reports ◽

10.1038/s41598-020-80931-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Takaya Ozeki ◽

Shoichi Maruyama ◽

Toshiyuki Imasawa ◽

Takehiko Kawaguchi ◽

Hiroshi Kitamura ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Renal Biopsy ◽

Focal Segmental Glomerulosclerosis ◽

Clinical Diagnosis ◽

Clinical Characteristics ◽

Minimal Change Disease ◽

Multivariable Analysis ◽

Laboratory Data ◽

Minimal Change ◽

Segmental Glomerulosclerosis

AbstractFocal segmental glomerulosclerosis (FSGS) is a serious condition leading to kidney failure. We aimed to investigate the clinical characteristics of FSGS and its differences compared with minimal change disease (MCD) using cross-sectional data from the Japan Renal Biopsy Registry. In Analysis 1, primary FSGS (n = 996) were stratified by age into three groups: pediatric (< 18 years), adult (18–64 years), and elderly (≥ 65 years), and clinical characteristics were compared. Clinical diagnosis of nephrotic syndrome (NS) was given to 73.5% (97/132) of the pediatric, 41.2% (256/622) of the adult, and 65.7% (159/242) of the elderly group. In Analysis 2, primary FSGS (n = 306) and MCD (n = 1303) whose clinical diagnosis was nephrotic syndrome (NS) and laboratory data were consistent with NS, were enrolled. Logistic regression analysis was conducted to elucidate the variables which can distinguish FSGS from MCD. On multivariable analysis, higher systolic blood pressure, higher serum albumin, lower eGFR, and presence of hematuria associated with FSGS. In Japanese nationwide registry, primary FSGS patients aged 18–64 years showed lower rate of NS than those in other ages. Among primary nephrotic cases, FSGS showed distinct clinical features from MCD.

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