Unilateral nephrectomy and cisplatin as risk factors of ifosfamide-induced nephrotoxicity: analysis of 120 patients.

PURPOSE This study was performed to identify risk factors of ifosfamide-induced renal damage. PATIENTS AND METHODS Renal function was assessed in 120 patients at a minimum of 3 months after completion of chemotherapy including ifosfamide. The cumulative ifosfamide dose ranged from 2 to 95 g/m2 (median, 30 g/m2). Ten patients had undergone unilateral nephrectomy; combination cytostatic treatment included cisplatin in 51 and methotrexate in 57. Sixty-eight patients had received gentamicin treatment. The glomerular filtration rate was estimated using the Schwartz formula. Proximal tubular function was assessed by the percent reabsorptions of glucose and 16 amino acids, the fractional excretion of sodium, and the fractional reabsorption of phosphate. In addition, the serum bicarbonate level was measured. RESULTS Proximal tubular dysfunction--with a predominance of renal amino acid (66.3%) and phosphate loss (38.3%)--was much more frequent than both glomerular impairment and acidosis. Seven patients were identified as having renal Fanconi's syndrome, and generalized tubulopathy was noted in another 15 patients. Ifosfamide-induced nephrotoxicity was dose-dependent, with a weak linear inverse correlation between cumulative ifosfamide dose and fractional phosphate reabsorption. Unilateral nephrectomy proved to be the single most important risk factor (odds ratio for the development of renal Fanconi's syndrome, 11.4), but cisplatin also significantly enhanced ifosfamide-mediated nephrotoxicity. Methotrexate, gentamicin, and patient age at primary diagnosis had no influence on renal function. CONCLUSION Ifosfamide chemotherapy should probably be restricted in patients after unilateral nephrectomy.

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Disorders of tubular electrolyte handling

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0506 ◽

2020 ◽

pp. 5112-5123

Author(s):

Nine V.A.M. Knoers ◽

Elena N. Levtchenko

Keyword(s):

Serum Magnesium ◽

Serum Phosphate ◽

Magnesium Concentration ◽

Main Site ◽

Fanconi’S Syndrome ◽

Tubular Transport ◽

Bone Changes ◽

Proximal Tubular ◽

Magnesium Excretion ◽

Fanconi's Syndrome

Glycosuria—glucose reabsorption in the proximal tubule is carried out by two different pairs of apical Na+-dependent (SGLT1 and -2) and basolateral Na+-independent (GLUT1 and -2) glucose transporters. Abnormalities in renal glucose transport can be seen in association with other defects of proximal tubular transport. Familial renal glycosuria is a rare autosomal recessive condition caused by mutations in the SGLT2-encoding gene, SLC5A2. Phosphate-handling disorders—the plasma concentration of inorganic phosphate depends on the balance between intestinal absorption, renal excretion, and the internal contribution from bone. Changes of serum phosphate levels can be caused by numerous inherited and acquired conditions. Disorders associated with increased urinary phosphate excretion and low serum phosphate levels produce symptoms that mainly affect the bones: rickets in children and osteomalacia in adults. Magnesium-handling disorders—normal plasma magnesium concentration is achieved by variation of urinary magnesium excretion in response to altered uptake by the intestine. The main site of magnesium absorption is the small bowel, via paracellular simple diffusion at high intraluminal concentrations, and via active transcellular uptake through the magnesium channel TRPM6 at low concentrations. Regulation and fine-tuning of serum magnesium concentration occurs primarily in the kidney. Genetic disorders of magnesium handling include Gitelman’s syndrome. Aminoaciduria and renal Fanconi’s syndrome—most amino acids (except for tryptophan, which is protein bound) are freely filtered by the glomerulus, after which 95 to 99.9% are reabsorbed in the proximal tubules by apical Na+-dependent cotransporters and Na+-independent cotransporters. Aminoaciduria is defined as urinary excretion of more than 5% of the filtered load of an amino acid. Renal Fanconi’s syndrome is characterized by a generalized defect of both Na+-coupled and receptor-mediated proximal tubular transport.

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Tubular function

10.1093/med/9780199592548.003.0008 ◽

2015 ◽

Author(s):

Marijn Speeckaert ◽

Joris Delanghe

Keyword(s):

Fractional Excretion ◽

Tubular Function ◽

Tubular Dysfunction ◽

Renal Fanconi Syndrome ◽

Glomerular Function ◽

Diminished Capacity ◽

Fractional Excretion Of Sodium ◽

Proximal Tubular ◽

Pass Through ◽

Renal Tubular

Assessment of tubular function is more complicated than the measurement of glomerular filtration rate. Different functions may be affecting according to the different segments of tubule involved. Key tests include concentrating and diluting capacity, and fractional excretion of sodium. Tubular proteinuria occurs when glomerular function is normal, but when the proximal tubules have a diminished capacity to reabsorb and to catabolize proteins, causing an increased urinary excretion of the low-molecular-mass proteins that normally pass through the glomerulus. Proximal tubular dysfunction is characterized by hypophosphataemia, and a variety of other abnormalities characteristics of the renal Fanconi syndrome. Distinguishing the location of the lesion in Renal Tubular Acidosis is considered in Chapter 35.

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Reversible Proximal Tubular Dysfunction in a Patient with Acute Febrile Illness, Marked Hyperbilirubinemia and Normal Renal Function: Evidence of Leptospirosis

Nephron ◽

10.1159/000064304 ◽

2002 ◽

Vol 91 (3) ◽

pp. 532-533 ◽

Cited By ~ 4

Author(s):

Evagellos Liberopoulos ◽

Eleni Bairaktari ◽

Moses Elisaf

Keyword(s):

Renal Function ◽

Normal Renal Function ◽

Febrile Illness ◽

Tubular Dysfunction ◽

Acute Febrile Illness ◽

Proximal Tubular Dysfunction ◽

Proximal Tubular

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Acute tubulointerstitial nephritis with uveitis syndrome presenting as multiple tubular dysfunction including Fanconi's syndrome

Pediatric Nephrology ◽

10.1007/bf00866499 ◽

1992 ◽

Vol 6 (6) ◽

pp. 547-549 ◽

Cited By ~ 31

Author(s):

Takashi Igarashi ◽

Hidehiko Kawato ◽

Shigehiko Kamoshita ◽

Kazuo Nosaka ◽

Kouichi Seiya ◽

...

Keyword(s):

Tubulointerstitial Nephritis ◽

Tubular Dysfunction ◽

Acute Tubulointerstitial Nephritis ◽

Fanconi’S Syndrome ◽

Fanconi's Syndrome

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Increased risk of ifosfamide-induced renal Fanconi's syndrome after unilateral nephrectomy

The Lancet ◽

10.1016/0140-6736(93)90524-k ◽

1993 ◽

Vol 341 (8847) ◽

pp. 755 ◽

Cited By ~ 11

Author(s):

Rainer Rossi ◽

Almut Kleinebrand ◽

Almud Gödde ◽

Bettina Rath ◽

Herbert Jürgens

Keyword(s):

Unilateral Nephrectomy ◽

Fanconi’S Syndrome ◽

Increased Risk ◽

Fanconi's Syndrome

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MO177RENAL PROXIMAL TUBULAR DISORDER AND RENAL FUNCTION LOSS IN HIV-INFECTED PATIENTS TREATED WITH TENOFOVIR DISOPROXIL FUMARATE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab092.0055 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Bingbin Zhao ◽

Xiaoxiao Shi ◽

Tiantian Ma ◽

Jiaying Li ◽

Peng Xia ◽

...

Keyword(s):

Renal Function ◽

Tubular Dysfunction ◽

Proximal Tubular Dysfunction ◽

Decline Rate ◽

Proximal Tubular ◽

The Impact ◽

Annual Decline ◽

Egfr Decline

Abstract Background and Aims Tenofovir disoproxil fumarate (TDF), as the most common antiviral drug, can cause both proximal tubular transportation dysfunctions and eGFR decline. The relationship between them is not clear due to lack of clinical data from large cohorts, especially in the Chinese population. In this study, we summarized the characteristics of proximal tubular injuries and eGFR decline in the cohort of HIV-infected patients treated with TDF, and explore the the impact of tenofovir on tubular transporters in vitro. Method We enrolled HIV-infected patients treated with TDF, who were regularly followed up in our hospital from Sep 1, 2001 to August 31, 2019. Their baseline and follow-up clinical data were collected. Proximal tubular dysfunction was defined as meeting two or more of the following criteria: hypophosphatemia, hypouricemia, low carbon dioxide binding capacity, positive urine glucose with normal plasma glucose level, and positive urine protein. Rapid deterioration of renal function was defined as the annual decline rate of eGFR exceeding 5ml/min/1.73m2. We also used human renal proximal tubular epithelial cell line (HK2) to further investigate the impact of tenofovir on transporters including SGLT2, NaPi-IIa, and URAT1 through immunofluorescence. Results A total of 375 HIV-infected patients receiving TDF were enrolled, mainly males (90.1%), with a median follow-up duration of 34(17, 58) months. The most common clinical manifestations were proteinuria (20.3%) and hypophosphatemia (12.3%). The prevalence of proximal tubular injury was 6.7%, which was significantly associated with low body weight, but was not associated with age, TDF course, baseline viral load, or baseline CD4+ T lymphocyte count. Their eGFR levels at the end of the follow-up were significantly lower than the baseline levels (104.6±15.2 vs. 110.6±14.2 ml/min/1.73m2, P<0.001). The average annual decline rate of eGFR was 5.0± 22.7 ml/min/1.73m2, and 23.6% of our patients had an annual decline rate of eGFR exceeding 5 ml/min/1.73m2. Rapid deterioration of renal function (≥ 5 ml/min/1.73m2 per year) was significantly associated with female but not related to proximal tubular dysfunction in multivariate logistic regression analysis. In vitro, the survival rate of HK2 cells was more than 95% when treated with tenofovir with a concentration of 1μmol/L for 48h. The expression levels of transporters (SGLT2, URAT1, and NaPi-IIa) were declined under the condition. Conclusion Among the HIV-infected Chinese patients treated with TDF, 6.7% had proximal tubular dysfunction and 23.6% showed accelerated annual decline rate of eGFR (≥ 5 ml/min/1.73m2 per year).

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Reversible tubular dysfunction that mimicked Fanconi's syndrome in a patient with anorexia nervosa

International Journal of Eating Disorders ◽

10.1002/eat.1078 ◽

2001 ◽

Vol 30 (2) ◽

pp. 227-230 ◽

Cited By ~ 10

Author(s):

George Alexandridis ◽

George Liamis ◽

Moses Elisaf

Keyword(s):

Anorexia Nervosa ◽

Tubular Dysfunction ◽

Fanconi’S Syndrome ◽

Fanconi's Syndrome

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Idiopathic Adult Onset Fanconi’s Syndrome in a Patient Treated with Oxaliplatin

Austin Journal of Clinical Case Reports ◽

10.26420/austinjclincaserep.2021.1206 ◽

2021 ◽

Vol 8 (4) ◽

Author(s):

Nguyen A ◽

◽

Benz S ◽

Keyword(s):

Urine Analysis ◽

Signs And Symptoms ◽

Proximal Convoluted Tubule ◽

Adult Onset ◽

Tubular Injury ◽

Fanconi’S Syndrome ◽

Proximal Tubular ◽

Fanconi's Syndrome ◽

Electrolyte Replacement

Proximal tubular injury is known complication of chemotherapy such as carboplatin. However, there are far more other causes of injury and in many situations, the etiology is difficult to elucidate. Here we describe a case of a patient who presented with a urine analysis consistent of Fanconi’s syndrome with signs and symptoms of the disorder prior to chemotherapy but requiring admission for aggressive electrolyte replacement soon after the chemotherapy was completed. We further discuss causes of Fanconi’s syndrome and the importance of evaluation of the proximal convoluted tubule prior to administration of chemotherapy.

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