Acquired Fanconi syndrome secondary to light chain deposition disease associated with monoclonal gammopathy of renal significance: A case report.

RATIONALE: Renal Fanconi syndrome (FS) is a rare complication of monoclonal gammopathy. It is characterized by the impairment of renal proximal tubular function leading to normoglycemic glycosuria, aminoaciduria, hypophosphatemia, hypouricemia and proximal renal tubular acidosis. Renal impairment in monoclonal gammopathy, without fulfilling the criteria of multiple myeloma, is categorized as monoclonal gammopathy of renal significance (MGRS). PATIENT CONCERNS: A 54-year-old male presented with progressively aggravated bone pain and limitation of activity was admitted to our department. A proximal renal tubular damage was suggested by hypophosphatemia, compensated metabolic acidosis, renal glycosuria, aminoaciduria, and hypouricemia. M-protein of IgA kappa was detected by immunofixation electrophoresis. Mildly increased plasma cells were found in bone marrow cytomorphologic examination. Renal biopsy revealed diffuse linear monoclonal IgA-kappa light chain deposits along tubular basement membranes (TBMs), while lambda was negative. Electron microscopy showed granular electron-dense deposits along the outer aspect of TBMs. DIAGNOSES: The patient was diagnosed as FS induced osteomalacia secondary to monoclonal gammopathy of renal significance (MGRS) (IgA-κ type) and LCDD. INTERVENTIONS: He was treated with bortezomib, supplementation by phosphate, alkali agents, and active vitamin D. He responded well to the treatment symptomatically. OUTCOMES: We reported a rare case of adult acquired FS with hypophosphatemic osteomalacia secondary to LCDD associated with MGRS and the patient was successfully treated with bortezomib. LESSONS: Although few cases of LCDD with isolated symptoms of tubulointerstitial nephropathy, rather than glomerular symptoms have been reported. It still needs to be recognized as a differential diagnosis in monoclonal gammopathy.

[A Case of Tenofovir-associated Fanconi Syndrome in Patient with Chronic Hepatitis B].

Tenofovir disoproxil fumarate (TDF) is one of the most widely used treatment options for human immunodeficiency virus (HIV) and HBV infections. Despite its efficacy and safety, some cases of nephrotoxicity have been reported in the treatment of HIV patients. Even more recently, very few cases of Fanconi syndrome associated with tenofovir therapy in HBV monoinfection have been reported. Herein, we report a case of a 47-year-old male with an HBV monoinfection, who developed Fanconi syndrome and a secondary osteomalacia with multiple bone pain. After TDF withdrawal and supplementation of calcitriol, his renal function was reverted. Although the overall risk of TDF-associated nephrotoxicity is very low, both glomerular and tubular function should be monitored in patients undergoing TDF treatment.

Acquired fanconi syndrome with osteomalacia secondary to monoclonal gammopathy of undetermined significance.

A 60-year-old woman was admitted because of multiple bone pain. Examination revealed hypophosphatemic osteomalacia and acquired Fanconi syndrome. Further exploration revealed monoclonal gammopathy of undetermined significance (MGUS) excreting urinary Bence Jones protein (kappa light chain). Renal biopsy showed non-specific tubulointerstitial nephritis, yet neither crystalline inclusions in the cytoplasm of the tubular epithelium nor myeloma casts nor amyloid deposits were found. She was treated with supplementation by phosphate, alkali agents, and vitamin D, and responded well to the treatment symptomatically and biochemically. MGUS was observed without chemotherapy. Myeloma had not developed after 10 months follow-up.

Combined renal tubular acidosis and diabetes insipidus in hematological disease.

BACKGROUND: A 39-year-old male with multiple myeloma was admitted for treatment with melphalan and autologous stem cell reinfusion. He presented with hypokalemia and hyperchloremic non-anion-gap metabolic acidosis with a high urinary pH. He also had hypomagnesemia, hypophosphatemia, hypouricemia, proteinuria and glucosuria. The patient subsequently developed polyuria with a low urine osmolality, hypernatremia and, finally, acute renal failure. INVESTIGATIONS: Physical examination, blood and urine analyses, kidney biopsy and tonicity balance. DIAGNOSIS: Fanconi syndrome with proximal (type II) renal tubular acidosis caused by myeloma kidney. Renal tubular acidosis was complicated by probable nephrogenic diabetes insipidus and acute renal failure. MANAGEMENT: Potassium supplementation, sodium bicarbonate therapy, intravenous fluid therapy and dialysis.

Acquired fanconi syndrome induced by mixed Chinese herbs presenting as proximal muscle weakness.

We report a rare case with acquired Fanconi syndrome caused by mixed Chinese herbs, initially presenting as waddling gait and lower limb muscle atrophy. From a series of investigations, proximal renal tubule injury with functional defects and Chinese herb nephropathy were discovered. Hypophosphatemic osteomalacia and type II muscle fiber atrophy shown in muscle biopsy of left quadriceps may be associated with the sequelae of ingestion of mixed crude Chinese herbs. Aggressive and early alkali treatment with supplementation of phosphate and Vitamin D restored the patient's metabolic and musculoskeletal abnormalities.

Herbs and the kidney.

The use of herbal therapy has increased dramatically in past years and may lead to renal injury or various toxic insults, especially in renal patients. In most countries, herbal products are not regulated as medicines. Herbal poisoning may be secondary to the presence of undisclosed drugs or heavy metals, interaction with the pharmacokinetic profile of concomitantly administered drugs, or association with a misidentified herbal species. Various renal syndromes were reported after the use of medicinal plants, including tubular necrosis, acute interstitial nephritis, Fanconi's syndrome, hypokalemia or hyperkalemia, hypertension, papillary necrosis, chronic interstitial nephritis, nephrolithiasis, urinary retention, and cancer of the urinary tract. It seems critical that caregivers be aware of the potential risk of such often underreported therapy and carefully question their patients about their use of this popular branch of alternative medicine.

Outbreak of Chinese herb nephropathy in Japan: are there any differences from Belgium?

OBJECTIVE: The purpose of this article was to study and clarify the features of Chinese herb nephropathy (CHN) in Japan. PATIENTS AND METHODS: The subjects consisted of patients diagnosed as having CHN in Saiseikai Nakatsu Hospital and of those reported in the literature in Japan. We investigated the clinical and histological features of CHN patients in Japan and compared them with the Belgian cases. RESULTS: The remarkable differences were as follows: (1) high prevalence in males compared with Belgian cases, (2) Fanconi syndrome was found in most cases, (3) no patients had malignant tumors in the urinary tract. In addition, the ascribed Chinese medicines in Japan were divided into three groups: 'Tenshin-toki-shigyaku-ka-gosyuyu-syokyo-to', 'Boui-ougi-to', and others. CONCLUSION: CHN in Japan has some characteristics distinguished from Belgian nephropathy. One hypothesis is a susceptibility to aristolochic acids (AAs), which is considered to be a causative agent, may be different among races. Another is that there could be some other toxic substances affecting the clinical findings although they are not identified at present. Further studies must be undertaken to clarify these differences.

Chinese herb nephropathy in Japan presents adult-onset Fanconi syndrome: could different components of aristolochic acids cause a different type of Chinese herb nephropathy?

BACKGROUND: We encountered two cases of Chinese herb-induced Fanconi syndrome in Japan. One component of the chinese medicine was "Kan-mokutsu" (Aristolochia manshuriensis) in which aristolochic acids (AAs) were detected. METHODS: Renal biopsy showed flattening of proximal tubular epithelial cells and paucicellular interstitial fibrosis without glomerular lesions, all of which were in accordance with Chinese herb nephropathy (CHN). To date, many cases of CHN have been reported mainly as progressive renal failure in western countries. RESULTS: However, our cases were different from those in that they presented Fanconi syndrome. The detected AAs in our cases consisted of aristolochic acid (AA)-I, II and D. In contrast, in Belgium, the incriminated agent was Aristolochia fangchi which consisted of AA-I, B, C, and aristolactum. CONCLUSION: These findings could indicate that different components of AAs could cause different clinical lesions, or that the amount of ingested AAs might reflect clinical pictures, that is to say, our patients took lower volume of Chinese herbs and might be in an early stage of CHN. Furthermore, it is likely that susceptibility to this substance may be different among races. CHN would include two clinical aspects: subacute renal failure and adult-onset Fanconi syndrome. It is important to bear in mind that CHN could present Fanconi syndrome.

Acquired Fanconi's syndrome associated with monoclonal gammopathies.

Franconi's syndrome is a rare complication of the monoclonal gammopathies characterized by diffuse failure in reabsorption at the level of the proximal renal tubule resulting in glycosuria, generalized aminoaciduria, and hypophosphatemia. Current evidence suggests monoclonal light chains that are incompletely digested in renal tubule lysosomes cause renal injury. The light-chain fragments serve as a nidus for crystal formation, and the crystals interfere with a broad range of apical membrane transporters. Franconi's syndrome is predominantly associated with monoclonal kappa in the urine, but rare instances of FS caused by lambda light chains have been described. Overt hematologic malignancies such as multiple myeloma, Waldenström's macroglobulinemia, or other lymphoproliferative disorders occur in one third of patients. Clinical manifestations include slowly progressive renal failure and bone pain caused by osteomalacia. The osteomalacia is caused by chronic hypophosphatemia and may be exacerbated by secondary hyperparathyroidism and renal tubular acidosis. Treatment consists of supplementation with phosphorus, calcium, and vitamin D. The osteomalacia is often completely reversible with mineral supplementation. Patients with an associated symptomatic malignancy or rapidly progressive renal failure may also benefit from chemotherapy. The prognosis is good in the absence of overt malignant disease.

Aminoaciduria and glycosuria following severe childhood lead poisoning.

To determine the incidence of renal functional abnormalities after lead poisoning, we evaluated the parameters of renal tubular function in 134 children and young adults, 8-13 years after chelation therapy for severe lead poisoning. There was no evidence of hypertension or reduced kidney function as assessed by serum creatinine (Cr) concentrations. Urinary alpha-amino nitrogen (Uaan) concentrations were significantly increased compared with 19 healthy age-matched controls. Ninety-four children (70%) had aminoaciduria (Uaan/Cr >0.23). Urinary glucose excretion was also significantly higher than that of 2 historical controls. Thirty-two children (24%) had glycosuria (>125 mg/24 h). Fractional excretion of phosphate was normal in all children. We conclude that a partial Fanconi syndrome can persist up to 13 years after childhood lead poisoning.

Fanconi's syndrome in a dog with primary hypoparathyroidism.

An 11-year-old castrated male mixed breed dog was referred for evaluation of muscle twitching, polyuria, polydipsia, anorexia, and periocular alopecia. Primary hypoparathyroidism was diagnosed by documenting decreased serum concentrations of parathyroid hormone and ionized calcium. Neurological, gastrointestinal, and dermatological signs resolved after calcium repletion. Initially, 1,25-dihydroxycholecalciferol PO was required to correct the hypocalcemia. Dihydrotachysterol, in combination with oral calcium supplementation, was used for long-term maintenance of normal serum calcium concentration. Aminoaciduria, glucosuria, and hyperchloremic metabolic acidosis were consistent with a diagnosis of Fanconi's syndrome. This diagnosis was further supported by the presence of hypokalemia and increased urinary fractional excretion of sodium, potassium, calcium, phosphorus, and magnesium. Renal tubular dysfunction resolved after oral supplementation with calcium and vitamin D3. Fanconi's syndrome in this dog may have been caused by decreased serum concentration of 1,25-dihydroxycholecalciferol, which was secondary to decreased parathyroid hormone production.