FOCAL SEGMENTAL GLOMERULOSCLEROSIS AND MULTIPLE MYELOMA.

Wajih Ullah M 1 , Rehman A 2 , Ashraf F 3 , Siddiq W 4 , Latif Wa 5 , Prasai K 6 and Bai Joti 7 . 1. Card iology, Mayo Clin ic, Rochester, USA, 802 1st ST SW, Rochester, MN, USA. 2. Observer In Internal Medicine, Bay lor Saint Luke's Medical Center, Houston, USA. 3. Internal Medicine, Jinnah Sindh Medical University, Karachi, PAK. 4. Internal Medicine, Harvard Medical College/Beth Israel Deaconess Medical Center, Boston, USA. 5. Internal Medicine, Fat ima Jinnah Medical University, High Point, USA. 6. Oncology, Mayo Clinic, Rochester, MN, USA. 7. Internal Medicine, Liaquat University of Medical and Health Sciences Hospital Jamshoro Sindh Pakistan., Jamshoro, PAK. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History

Focal segmental glomerulosclerosis (FSGS) is one of the most important causes of end-stage renal disease in the United States. FSGS is more prevalent in young African A merican patients. It is common ly associated with various conditions such as genetic abnormalit ies, metabolic disorders, infections, and drug abuse. FSGS is a rare disease, and its association with hematological disorders is uncommon. In this study, we are documenting a case of the FSGS due to underlying mu ltip le myelo ma. The objective of this study is to emphasize the importance of excluding hematolog ic disorders in the older patients before diagnosing them with idiopathic FSGS. Early diagnosis and treatment of the underlying condition responsible for the FSGS can lead to complete remission of the FSGS, thus preventing complicat ions such as renal failure.

Introduction:-
Focal segmental glo merulosclerosis (FSGS) is one of the most important causes of end -stage renal disease in the United States. FSGS is more prevalent in young African A merican patients [1]. FSGS is responsible for nephrotic syndrome in 40% of adults [2]. Co mmon etio logies associated with FSGS are genetic abnormalit ies, metabolic disorders, infections and drug abuse [3]. Ho wever, FSGS has rarely been reported in association with hematologic malignancies such as lymphoproliferative, myeloproliferative and plasma cell disorders. In this study, we are documenting a case of FSGS in association with mult iple myelo ma in a 55-year-o ld male Asian patient.

Case Presentation:-
A 55-year-old male Asian patient was referred to the nephrology department by his primary care physician for the evaluation of incidental proteinuria. The patient experienced no associated symptoms such as fever, weight/appetite changes, cough, or any antecedent infection. His past medical, surgical and family history was unremarkable, and he had no modifiab le or non-modifiable risk factors. He never smoked cigarettes or used any illicit drugs. The physical examination revealed a b lood pressure of 170/ 100 mm Hg and +2 bilateral pitting edema in his lo wer limbs. The rest of the systemic examination was unremarkable.

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The patient was asked to follow-up with his urine and blood tests. Laboratory investigations revealed creatinine 1.3 mg/dl, blood urea nitrogen (BUN) 20 mg/dl and proteinuria 2400 mg/24 hours. The patient was admitted to the hospital for additional investigations. The patient was administered angiotensin-converting enzyme inhibitor (ACEI) to control his high blood pressure. Additionally, he was scheduled for a renal biopsy. The patient was diagnosed with FSGS based on his histopathological findings. At his follow -up visit one month later, the patient's high blood pressure was controlled. Ho wever, proteinuria and serum creatin ine were slightly increased.
Seven months after his last visit, the patient visited the hospital again for a co mplaint of back pain for the last one month. The pain was constant, dull, 6/ 10 in intensity, aggravated by movement and occurs at night. An X-ray of the spine revealed lytic lesions on the lumbar spine. Laboratory investigations revealed serum calciu m levels of 14.5 mg/dl (calciu m normal levels 8.5-12.2 mg/dl). Considering the probability of mult iple myelo ma, a urine protein electrophoresis was ordered and the patient was scheduled for a bone marrow aspiration and biopsy. The electrophoresis revealed light chains in immunofixation of urine. Bo ne marro w aspiration and biopsy revealed more than 35% kappa positive plasma cells. Based on the clinical features, pathological findings, and investigations, the patient was diagnosed with mult iple myelo ma. The patient was started on thalidomide, dexameth asone, and pamidronate. After two weeks of his treatment, the calciu m level came down to normal and the patient felt a considerable improvement in his back pain as well. In the follo wing visit, his proteinuria had also decreased and repeated biopsy of the kidney showed resolution of the FSGS.

Discussion:-
FSGS is a type of glomeru lar disease and is characterized by sclerosis in small sections of each glomerulus. It is one of the most important causes of end-stage renal disease. FSGS is associated with various etiologies, which are summarized below in figure 1.

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Histologically, FSGS is defined as the segmental obliteration of glo merular capillaries by the extracellu lar matrix [4][5]. The histologic variants of the FSGS are described in figure 2 [6]. In our case report, the patient was diagnosed with the FSGS based on his clinical and histopathological fin dings. The patient was diagnosed with tip variant FSGS, wh ich has a good prognosis and higher remission rates compared with other variants [7]. FSGS is commonly seen in young African Americans with conditions like genetic abnormalit ies, metabolic disorders, infect ions, or drug abuse. However, the association of the FSGS with hematologic malignancies is rarely seen especially in the older Asian population [2]. Few studies have documented that the FSGS and hematologic malignancies are epidemiological and temporally linked.
Shah S et al. in his study reported a case of collapsing FSGS in association with mult iple myelo ma that underwent partial remission follo wing the treatment for the underlying disease [8]. Similarly, in another retrospective study by Dingli D et al. identified 13 patients with the FSGS and a monoclonal plasma cell disorder. Out of 13 patients, four patients had mult iple myelo ma and nine patients had monoclonal gammopathy of undetermined significance.

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Patients treated for multiple myelo ma experienced improvement in their renal lesion, and the latter relapsed when the mult iple myelo ma relapsed [3]. In another study by Calvo JV et al. they discovered an association between FSGS and non-Hodgkin's lympho ma [9].Similarly, one study published by Ashrafi F et al. reported a case report of FSGS who developed the manifestation of amylo idosis in his course of disease. Following urine protein electrophoresis and bone marrow study confirmed the diagnosis of mu ltip le myelo ma [10].
The authors of the above-mentioned studies concluded that before diagnosing patients with Idiopathic FSGS, especially adults and the elderly, hematologic disorders (especially plasma cell d isorders) must be excluded. The occurrence of these two conditions may not be as a result of chance [3]. In our patient, after init iation of treat ment for mult iple myelo ma, h is proteinuria decreased and FSGS resolved afterward. Thus, early diagnosis and treat ment of the underlying disease responsible for the FSGS can reduce the chances of the renal co mplications due to FSGS.

Conclusion:-
FSGS is a rare disease, and its association with hematological disorders is rarer. In this study, we want to highlight that in older patients, hematologic disorders must be ruled out before diagnosing them with idiopathic FSGS. This is because early diagnosis and treatment of the underlying condition responsible for FSGS can co mpletely resolve FSGS and prevent its complications.