Tubulointerstitial nephritis in methylmalonic acidemia

Rutledge, S. Lane; Geraghty, Michael T.; Mroczek, Ewa; Rosenblatt, D.; Kohout, Elfriede

doi:10.1007/bf00861581

Cited by 53 publications

(29 citation statements)

References 4 publications

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“…Intracellular cystine deposition associated with a lysosomal defect seems to be the primary mechanism in nephropathic cystinosis [22]and may be overcome by cysteamine treatment [34]. Toxic mechanisms may also be involved in tubulo-interstitial nephritis of methylmalonic aciduria [30]. Hydronephrosis related to excessive fluid intake was probably the reason for CRF that we observed in a child with nephrogenic diabetes insipidus.…”

Section: Discussionmentioning

confidence: 78%

“…A third group of HTD leading to CRF in more than 80% of the patients was characterized by renal deposition of nephrotoxic material . It includes Fanconi-Bickel syndrome [17], primary hyperoxaluria [29], and methylmalonic aciduria [30]. In each of these conditions and in primary Fanconi syndrome [16], we encountered at least 4 cases with CRF or ESRD.…”

Section: Discussionmentioning

confidence: 99%

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Long-Term Outcome of Paediatric Patients with Hereditary Tubular Disorders

Haffner

Weinfurth²,

Manz³

et al. 1999

Nephron

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Background: An increasing number of children with hereditary tubular disorders (HTD) reach adult life due to diagnostic and therapeutic advances which results in growing need to manage these patients by adult centres. Data on the prevalence and the late clinical problems of these patients are limited. Methods: We observed 177 paediatric patients with isolated or complex HTD between 1969 and 1994. The median age at the time of diagnosis was 3 (range 0–18) years and the median observation period 10 (range 1–43) years. The long-term outcomes with respect to renal function, bone disease, and body growth were analyzed. Results: The prevalence of HTD was 3.2% of all patients observed in our renal unit and 14% of those patients with chronic renal failure and/ or end-stage renal disease. The three most frequent disorders observed were nephropathic cystinosis (n = 34), X-linked hypophosphataemic rickets (n = 26), and idiopathic hypercalciuria (n = 17). At the last observation, 12% of the patients with isolated HTD and 30% of those with complex HTD had developed preterminal chronic renal failure; end-stage renal disease was observed in 5 and 25%, respectively (p < 0.001). Progressive disease occurred mainly in patients having cystinosis, primary hyperoxaluria, the syndrome of hypomagnesaemia/hypercalciuria, primary Fanconi syndrome, Fanconi-Bickel syndrome, and methylmalonic aciduria. Nephrocalcinosis was found in 42%, urolithiasis in 14%, bone deformities and/or fractures in 28%, and other extrarenal alterations in 29% of all patients. The median body height at last observation was 2.0 SD below the normal mean (range from –10.4 to +2.6), and the adult height was subnormal in 48% of 67 grown-up patients. Growth retardation was more severe in complex than in isolated HTD. The mortality decreased from 17% in 1969–1981 to 12% in 1982–1994. Conclusion: Although HTD are rare nephropathies, their frequently progressive course associated with extrarenal complications requires the attention of nephrologists beyond the paediatric age.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Long-Term Outcome of Paediatric Patients with Hereditary Tubular Disorders

Haffner

Weinfurth²,

Manz³

et al. 1999

Nephron

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“…Microscopy in these rats revealed that glomeruli appeared normal, whereas tubuli were dilated and tubulus epithelium showed mitochondrial swelling and disorganization of cristae. Although this study demonstrated some similarities with renal failure in methylmalonic acidurias considered to start with renal tubular dysfunction and tubulointerstitial nephritis [28,29], it remains unclear whether this animal model is suitable for the investigation of MMA-induced renal failure [27]. Such investigations should also refer to the tissue-specific differences regarding the vulnerability to specific toxins and mechanisms.…”

Section: Methylmalonic Acid and Renal Failurementioning

confidence: 88%

Methylmalonic acid — an endogenous toxin?

Kölker

Okun

2005

CMLS, Cell. Mol. Life Sci.

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Methylmalonic acid was previously considered as major neurotoxin in methylmalonic acidurias. In contrast, recent studies support the notion that other metabolites deriving from propionyl-coenzyme A, inducing synergistic inhibition of mitochondrial energy metabolism, are more important than methylmalonic acid to understand the neuropathogenesis of this disease. However, it is not yet known whether methylmalonic acid is involved in the induction of other organ manifestations in this disease, such as chronic renal failure.

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“…Tubulointerstitial nephritis and progressive renal function impairment have been associated with MMA (Rutledge et al 1993). There are several reports of combined liverkidney transplantation in patients with MMA (Nagarajan et al 2005;Kasahara et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Successful Domino Liver Transplantation from a Patient with Methylmalonic Acidemia

et al. 2015

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Liver transplantation has been reported in patients with methylmalonic acidemia (MMA), but longterm outcome is controversial. Many patients with other approved indications for liver transplantation die before donor grafts are available. A 28-year-old man with MMA underwent cadaveric liver transplantation. His liver was used as a domino graft for a 61-year-old man with primary sclerosing cholangitis, who had low priority on the transplant waiting list. Surgical outcome was successful, and after transplantation both patients have excellent graft function. The patient with MMA showed substantial decrease in methylmalonate in urine (from 5,277 AE 1,968 preoperatively to 1,068 AE 384 mmol/mol creatinine) and plasma (from 445.9 AE 257.0 to 333.3 AE 117.7 mmol/l) over >1-year follow-up, while dietary protein intake increased from 0.6 to 1.36 AE 0.33 g/kg/day. The domino recipient maintained near-normal levels of plasma amino acids but did develop elevated methylmalonate in blood and urine while receiving an unrestricted diet (peak plasma methylmalonate 119 mmol/l and urine methylmalonate 84-209 mmol/mol creatinine, with 1.0-1.9 g/kg/day protein). Neither patient demonstrated any apparent symptoms of MMA or metabolic decompensation during the postoperative period or following discharge.Conclusion: Liver transplantation substantially corrects methylmalonate metabolism in MMA and greatly attenuates the disease. In this single patient experience, a liver from a patient with MMA functioned well as domino graft although it did result in subclinical methylmalonic acidemia and aciduria in the recipient. Patients with MMA can be considered as domino liver donors for patients who might otherwise spend long times waiting for liver transplantation.

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Tubulointerstitial nephritis in methylmalonic acidemia

Cited by 53 publications

References 4 publications

Long-Term Outcome of Paediatric Patients with Hereditary Tubular Disorders

Long-Term Outcome of Paediatric Patients with Hereditary Tubular Disorders

Methylmalonic acid — an endogenous toxin?

Successful Domino Liver Transplantation from a Patient with Methylmalonic Acidemia

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