• Childhood Kidney Diseases
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• v.14 no.2
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• pp.120-131
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• 2010

Renal tubular acidosis (RTA) is a metabolic acidosis due to impaired excretion of hydrogen ion, or reabsorption of bicarbonate, or both by the kidney. These renal tubular abnormalities can occur as an inherited disease or can result from other disorders or toxins that affect the renal tubules. Disorders of bicarbonate reclamation by the proximal tubule are classified as proximal RTA, whereas disorders resulting from a primary defect in distal tubular net hydrogen secretion or from a reduced buffer trapping in the tubular lumen are called distal RTA. Hyperkalemic RTA may occur as a result of aldosterone deficiency or tubular insensitivity to its effects. The clinical classification of renal tubular acidosis has been correlated with our current physiological model of how the nephron excretes acid, and this has facilitated genetic studies that have identified mutations in several genes encoding acid and base ion transporters. Growth retardation is a consistent feature of RTA in infants. Identification and correction of acidosis are important in preventing symptoms and guide approved genetic counseling and testing.

• Electrolytes & blood pressure
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• v.16 no.2
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• pp.19-22
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• 2018

Renal Fanconi syndrome (RFS) is caused by generalized proximal tubular dysfunction and can be divided into hereditary and acquired form. Adult-onset RFS is usually associated with drug toxicity or systemic disorders, and modern molecular genetics may explain the etiology of previous idiopathic cases of RFS. Here, we report the case of a 52-year-old woman with RFS whose etiology could not be identified. She presented with features of phosphaturia, renal glucosuria, aminoaciduria, tubular proteinuria, and proximal renal tubular acidosis. Her family history was unremarkable, and previous medications were nonspecific. Her bone mineral density was compatible with osteoporosis, serum intact parathyroid hormone level was mildly elevated, and 25(OH) vitamin D level was insufficient. Her blood urea nitrogen and serum creatinine levels were 8.4 and 1.19 mg/dL, respectively (estimated glomerular filtration rate, $53mL/min/1.73m^2$). Percutaneous renal biopsy was performed but revealed no specific renal pathology, including mitochondrial morphology. No mutation was detected in EHHADH gene. We propose the possibility of involvement of other genes or molecules in this case of adult RFS.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.41-46
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• 2002

Effect of cadmium (Cd) intoxication on renal acid-base regulation was studied in adult male Sprague-Dawley rats. Cd intoxication was induced by subcutaneous injections of $CdCl_2$ at a dose of 2 mg Cd/kg/day for $3{\sim}4$ weeks. In Cd-intoxicated animals, arterial pH, $PCO_2$ and plasma bicarbonate concentration decreased, showing a metabolic acidosis. Urine pH and urinary bicarbonate excretion increased and titratable acid excretion decreased with no change in ammonium excretion. In renal cortical brush-border membrane vesicles derived from Cd-exposed animals, the $Na^+/H^+$ antiporter activity was significantly attenuated. These results indicate that chronic exposures to Cd impair the proximal tubular mechanism for $H^+$ secretion (i.e., $Na^+/H^+$ antiport), leading to a metabolic acidosis.

• Journal of Veterinary Clinics
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• v.22 no.4
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• pp.420-423
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• 2005

A 2-year-old 16-kg, intact female lindo was presented with weight loss and poor hair coat. Abnormal serum biochemical values included mild hypokalemia (3.9 mmol/L, reference range 4.37 to 5.35 mmol/L) and mild hyperglycemia (124 mg/dl, reference range 65 to 118 mg/dl). in the complete blood count and diagnostic imaging examination, abnormal changes wer not seen. The analysis of urine sample obtained from cystocentesis revealed glucosuria (> 100 mg/dl) and mild proteinuria. Repeated analysis after admission showed persistent glucosuria and hypokalemia. But blood glucose values did not exceed the renal threshold fur glucose reabsorption. To differentiate cause of the glucosuria, the glucose tolerance test and the low-dosage dexamethasone suppression test were indicated. Results of both tests were normal. In addition, the serum total thyroxine $(T_4)$ value was within normal range. The arterial blood gas analysis showed no remarkable changes. The fractional reabsorption rates of amino acids and phosphorus were calculated above $97\%$. Based on these findings, the dog was diagnosed as renal glucosuria due to proximal renal tubular dysfunction. But this persistent renal glucosuria with hypokalemia may be the initial sign of Fanconi's syndrome or proximal renal tubular acidosis.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.1
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• pp.69-76
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• 1998

Cis-diamminedichloroplatinum II (cisplatin), an effective antitumor agent, induces acute renal failure by unknown mechanisms. To investigate direct toxic effects of cisplatin in the renal proximal tubular transport system, OK cell line was selected as a cell model and $Na^+/H^+$ antiport activity was evaluated during a course of cisplatin treatment. The cells grown to confluence were treated with cisplatin for 1 hour, washed, and incubated for up to 48 hours. At appropriate intervals, cells were examined for $Na^+/H^+$ antiport activity by measuring the recovery of intracellular pH (pHi) after acid loading. Cisplatin of less than 50 ${\mu}M$ induced no significant changes in cell viability in 24 hours, but it decreased the viability markedly after 48 hours. In cells exposed to 50 ${\mu}M$ cisplatin for 24 hours, the $Na^+-dependent$ pHi recovery (i.e., $Na^+/H^+$ antiport) was drastically inhibited with no changes in the $Na^+-independent$ recovery. Kinetic analysis of the $Na^+-dependent$ pHi recovery indicated that the Vmax was reduced, but the apparent Km was not altered. The cellular $Na^+$ and $K^+$ contents determined immediately before the transport measurement appeared to be similar in the control and cisplatin group, thus, the driving force for $Na^+-coupled$ transport was not different. These results indicate that cisplatin exposure impairs the $Na^+/H^+$ antiport capacity in OK cells. It is, therefore, possible that in patients treated with a high dose of cisplatin, proximal tubular mechanism for proton secretion (hence $HCO_3^-$ reabsorption) could be attenuated, leading to a metabolic acidosis (proximal renal tubular acidosis).

• Journal of The Korean Society of Inherited Metabolic disease
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• v.1 no.1
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• pp.23-27
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• 2001

Fanconi-Bickel Syndrome (FBS) is a rare autosomal recessive disorder of carbohydrate metabolism recently demonstrated to be caused by mutations in the GLUT 2 gene for the glucose transporter protein 2 expressed in liver, pancreas, intestine, and kidney. This disease is characterized by hepatorenal glycogen accumulation, both fasting hypoglycemia as well as postprandial hyperglycemia and hyperglactosemia, and generalized proximal renal tubular dysfunctions. We report the first Korean patient with FBS diagnosed based on clinical manifestations and identification of a novel mutation in the GLUT 2 gene. She was initially diagnosed having a neonatal diabetes mellitus due to hyperglycemia and glycosuria at 3 days after birth. In addition, newborn screening for galactosemia revealed hypergalactosemia. Thereafter, she has been managed with lactose free milk, insulin therapy. However, she failed to grow and her liver has been progressively enlarging. Her liver functions were progressively deteriorated with increased prothrombin time. Liver biopsy done at age 9 months indicated micronodular cirrhosis with marked fatty changes. She succubmed to hepatic failiure with pneumonia at 10 months of age. Laboratory tests indicated she had generalized proximal renal tubular dysfuctions; renal tubular acidosis, hypophosphatemic rickets, and generalized aminoaciduria. Given aforementioned findings, the diagnosis of FBS was appreciated at age of 2 months. The DNA sequencing analysis of the GLUT 2 gene using her genomic DNA showed a novel mutation at 5th codon; Lysine5 Stop (K5X).

• Childhood Kidney Diseases
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• v.10 no.1
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• pp.58-64
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• 2006

In the clinical state of vitamin D deficiency, it is possible that associated phosphate depletion, parathyroid hormone excess, and hypocalcemia may all depress the proximal tubular reabsorption of bicarbonate, in addition to abnormal skeletal modeling or remodeling, Although nutritional rickets is considered a rare disease in developed countries nowadays, cases of vitamin D deficient rickets caused by various unhealthy lifestyles such as insufficient exposure to sunlight, breast feeding infants without giving vitamin D supplements, unbalanced vegetarian diets of breast feeding mothers, low-birth weight, and maternal deficiency of vitamin D or calcium are increasing. Here, we present the case of an 8 month old girl, who was completely breastfed without any weaning diet or infant vitamin supplements. She visited our emergency room with hypocalcemic seizure and subsequently was diagnosed with vitamin D deficient rickets accompanied by overt bone changes and proximal renal lobular acidosis. After intravenous(IV) and oral calcium replacement therapy(IV calcium gluconate injection 1 mEq/kg/day for 6 days, 2 mEq/kg/day for 4 days followed by oral calcium gluconate administration 4 g/day for 3 days) with vitamin D supplement(Alfacalcidol 0.5 mcg/day) during admission, serum calcium level was normalized with clinical improvement. Oral sodium bicarbonate(0.6 g/day) was administered from the $2^{nd}$ hospital day for 2 weeks, which normalized the serum bicarbonate(measured by $tCO_2$) level. Calcium and vitamin D replacement were continued for 2 weeks and 3 months each. After discontinuing medications, follow up laboratory findings showed good maintenance of serum calcium, alkaline phosphate and bicarbonate levels with complete improvement of bone X-ray findings.

• Clinical and Experimental Pediatrics
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• v.57 no.3
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• pp.140-148
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• 2014

Purpose: Lowe syndrome is a rare, X-linked recessive disorder caused by mutations in the OCRL gene. It involves multiple anatomic systems, particularly the eyes, central nervous system, and kidneys, and leads to profound growth failure and global developmental delay. This study evaluated the clinical and genetic characteristics of Korean patients with Lowe syndrome. Methods: The clinical findings and results of genetic studies were reviewed for 12 male patients diagnosed with Lowe syndrome at a single medical institution. Results: The mean age of the patients at presentation was 2.2 months (range, 0-4 months), although the diagnosis was delayed by a mean of 2.8 years (range, 0-9.7 years). The mean follow-up period was 9.0 years (range, 0.6-16.7 years). Nine mutations in OCRL were identified in 11 patients (92%), with three novel mutations. The main presentation was congenital cataract in both eyes necessitating early cataract removal in the 11 patients with impaired visual acuity. Profound short stature and developmental delay were observed in all patients, and seizures occurred in 50% of the patients. All patients suffered from proximal renal tubular dysfunction, and one patient developed chronic renal failure. Other manifestations included pathologic fracture (50%), cutaneous cysts (42%), and cryptorchidism (42%). However, there was no bleeding tendency, and none of the patients died during the study period. Conclusion: This study describes the clinical and genetic characteristics of Korean patients with Lowe syndrome. The observations are helpful for understanding the natural courses of Lowe syndrome and for appropriate genetic counseling.