Skip Navigation



NDT Advance Access published online on June 7, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm307
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
22/10/2879    most recent
gfm307v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Sharma, A. P.
Right arrow Articles by Filler, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sharma, A. P.
Right arrow Articles by Filler, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Incomplete distal renal tubular acidosis affects growth in children

Ajay P. Sharma1, Raj K. Sharma3, Rakesh Kapoor4, Alik Kornecki2, Saubhik Sural3 and Guido Filler1

1Department of Paediatrics, Division of Nephrology, 2Department of Paediatrics, Division of Critical Care Medicine, University of Western Ontario, London, Canada, 3Department of Nephrology and 4Department of Urology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India

Correspondence and offprint requests to: Dr Ajay Sharma, E6-123, WT, 800, Commissioner's Road E, London Health Sciences Centre, London, ON, Canada N6A5W9. Email: ajay.sharma{at}lhsc.on.ca



   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgements
 References
 
Background. Incomplete distal renal tubular acidosis (idRTA) is recognized as an underlying aetiology in recurrent nephrolithiasis. Until the recently reported high prevalence of idRTA in adults with osteoporosis, the effect of idRTA on skeletal parameters was not known. We hypothesize that idRTA has a potential to affect height in the paediatric population.

Methods. In a cross-sectional study, the children with posterior urethral valves (PUV), with normal estimated glomerular filtration rates, were evaluated for idRTA and complete dRTA. The idRTA evaluation was done by short ammonium chloride acidification test. The height standard deviation scores (SDS) in the idRTA group were compared with PUV children without dRTA, with complete dRTA, and to age and gender matched controls with no renal issue (n = 50).

Results. The idRTA group (n = 17) manifested a significantly lower mean height SDS (–1.94 ± 0.41 vs –0.46 ± 0.28; P < 0.001) and a higher short stature prevalence (height SDS below 2) (18% vs 0; P = 0.06) as compared with those without dRTA (n = 23). The matched controls showed a significantly higher height SDS as compared with the idRTA group (–0.39 ± 0.25 vs –1.94 ± 0.41; P < 0.001). As compared with the complete dRTA group (n = 9), the children with idRTA did have significantly higher height SDS (–1.94 ± 0.41 vs –5.31 ± 1.95; P = 0.002), and a lower short stature prevalence (18% vs 78%; P = 0.001). On multivariate analysis, dRTA was significantly associated with the height SDS (= –0.88; P < 0.001).

Conclusions. Incomplete dRTA affects height in children. This observation needs validation in longitudinal studies.

Keywords: children; clinical manifestations; distal renal tubular acidosis; height scores; posterior urethral valves



   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 Acknowledgements
 References
 
Renal tubular acidosis (RTA) syndromes result in a systemic metabolic acidosis disproportionate to a decrease in glomerular filtration rate. The renal tubular defects could be in the excretion of hydrogen ion (H+), as in distal RTA (dRTA), or in the reabsorption of bicarbonate (HCO3–), as in proximal (type 2) RTA. Distal RTA is further sub-classified into type 1 or type 4 RTA based on the mechanism responsible for H+ excretion defect [1,2].

A complete dRTA is characterized by an inability to increase urinary H+ excretion despite a systemic hyperchloraemic metabolic acidosis [1]. In contrast, incomplete dRTA (idRTA) does not manifest a metabolic acidosis under basal conditions; however, there remains an inability to acidify urine, which can be demonstrated in context of an induced systemic metabolic acidosis under controlled conditions [1].

Complete dRTA is known to induce systemic manifestations including short stature, rickets, hypercalciuria and nephrocalcinosis due to chronic systemic metabolic acidosis [3–6]. Growth retardation is a major clinical issue in the children with complete primary dRTA [5,6]. The clinical effects of idRTA have been limited to its recognized association with recurrent nephrolithiasis and nephrocalcinosis [7,8]. Unlike complete dRTA, idRTA was not suspected to induce skeletal effects until the recently reported prevalence of idRTA in 30% of adults with osteopenia [9] and in 19% with osteoporosis [10]. Due to major skeletal growth in the paediatric age group, the clinical manifestations due to idRTA can be more severe in the childhood period; however, an association between idRTA and somatic growth has not been systematically investigated.

To test our hypothesis, we retrospectively looked at our prospectively collected data to evaluate a possible association between idRTA and the height scores in boys with posterior urethral valves (PUV). The study group was selected due to previously reported high idRTA prevalence in this population [11,12].



   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 Acknowledgements
 References
 
Patients
The newly diagnosed children with PUV, who manifested a preserved estimated glomerular filtration rate (eGFR) after the surgical intervention, were included in the study [13]. The reasons for the referral included persistent voiding symptoms, repeated urinary tract infections (UTI), antenatal or incidental hydronephrosis, renal failure or already diagnosed PUV. The patients were on no treatment except antibiotic prophylaxis (cotrimoxazole) in five children due to recurrent UTI. Age- and gender-matched controls, with no renal issue, were selected from pre-surgery clinics.

Study period and venue
Patients were referred from January 1996 to July 2003 to Sanjay Gandhi Post-Graduate Institute (SGPGI), which is a tertiary care university hospital in India.

Exclusion criteria
A persistent renal insufficiency after surgery, or short stature diagnosed due to an alternative aetiology were reasons for exclusion from the study.

Study design
The diagnosis of PUV was confirmed on voiding cystourethrography. The data of duration of voiding symptoms prior to the surgery, age at surgery, presence and grade of VUR was collected. VUR was graded from I to V according to the criteria established by the International Reflux Study in Children [14]. The study group underwent an evaluation for complete and incomplete dRTA following the surgical intervention, after resolution of post-obstructive diuresis. The dRTA associated clinical manifestations (rickets, short stature and nephrocalcinosis), serum electrolytes, calcium, urate and phosphate, and urinary calcium, creatinine and electrolytes were recorded.

Definitions
Age at surgery
Age at the time of first surgical intervention (vesicostomy or fulguration) for PUV.

Duration of voiding symptoms
The duration since the voiding symptoms were first noticed prior to the surgery.

Renal insufficiency
eGFR was estimated by Schwartz method based on serum creatinine measured by Jaffe first-order kinetic reaction on RA 1000 auto analyser [13]. An eGFR ≥90 ml/min/1.73 m2 was considered normal.

DRTA evaluation
Evaluation for dRTA was done shortly after resolution of post-obstructive diuresis following the surgical intervention, in the absence of a UTI, ketoacidosis, or urinary sodium <25 mmol/l. None of the patients were treated with a potassium-sparing diuretic, trimethoprim–sulphamethoxazole, pentamidine, angiotensin-converting enzyme (ACE) inhibitor, steroid, thyroid hormone or sodium bicarbonate at the time of the evaluation. A complete dRTA was diagnosed by a basal systemic normal anion gap metabolic acidosis and positive urinary anion gap (Na + K – Cl) [1,15]. A blood pH <7.30 and serum bicarbonate <18 mmol/l, on two separate occasions, qualified for a basal metabolic acidosis. Complete dRTA was further sub-classified based on urine pH and serum potassium levels [2]. Urine pH was measured by a pH meter on a urine sample collected under oil. In children with serum potassium ≥5.5, a urinary transtubular potassium gradient TTKG = urine potassium/(urine osmolality/serum osmolality)/serum potassium was calculated.

In the absence of a basal metabolic acidosis, an evaluation for idRTA was conducted by ammonium chloride acidification test. Ammonium chloride was administered orally in a dose of 100 mg/kg [16], in a gelatin capsule or a powder form depending on patient's age or preference. A satisfactory response was a blood pH <7.30 and serum bicarbonate <18 mmol/l on a venous blood gas (VBG). The test was repeated with the same dose in children, who did not tolerate the first dose. In the absence of a satisfactory response to the first dose, the test was repeated with double the dose. Urine pH was assessed at baseline, 2, 4 and 6 h after ammonium chloride administration. An incomplete dRTA was diagnosed in the presence of urine pH persistently higher than 5.5, despite an induced systemic acidosis [9,10,16,23].

In 10 randomly selected samples, the correlation (R2) between VBG and arterial blood gases was 0.95 to 0.98, except for a significant difference in pO2.

Growth assessment
Height or length was measured using a stadiometer or an infantometer. Height and weight were expressed as standard deviations scores (SDS). SDS was calculated (subject height–mean height/SD of mean) from the growth chart references, developed from a population with socio-economic status and ethnic characteristics similar to the study group [17,18]. Short stature was diagnosed in the presence of a height SDS score below 2. All the children with short stature underwent a complete evaluation for alternative aetiologies by subspecialists including an endocrinologist and a gastroenterologist.

Rickets
Rickets was diagnosed in the presence of widened and irregular epiphyseal–metaphyseal junctions on X-rays of wrists and long bones by a radiologist blinded to the study [5,6].

Nephrocalcinosis and hypercalciuria
Nephrocalcinosis was diagnosed in the presence of the ultrasound evidence, reported by a radiologist blinded to the study. Urinary calcium, creatinine and other electrolytes were assessed on a regular diet, with no calcium or vitamin D supplementation, on a second morning urine sample. Hypercalciuria was defined by spot urine calcium to creatinine ratio greater than the upper level for the age [19,20].

Statistical analysis
Normality of the data was assessed by Kolmogorov–Smirnov test. Chi-square analysis was used for comparison of nominal data. Continuous variables between two groups were compared by unpaired t-test, if normally distributed, and by Mann–Whitney U-test otherwise. Multiple group comparison was done by Kruskal–Wallis test. Univariate and stepwise multivariate regression analysis was used to calculate regression coefficients. Correlation was done using Spearman's correlation analysis. Statistical differences were considered significant at P <0.05. SPSS version 11.0 (SPSS, Inc., Chicago, IL, USA) software package was used for the statistical calculations. The study protocol was approved by the local research committee. A verbal informed consent was obtained in the presence of overt metabolic acidosis; the study participants with no overt metabolic acidosis provided written informed consent prior to the study enrolment.



   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 Acknowledgements
 References
 
Fifty-five children with PUV were reviewed during the study period. Six children were excluded; five due to persistent eGFR <60 ml/min/1.73 m2 after surgical intervention and one due to a short stature secondary to hypothyroidism. Finally, 49 children constituted the study group.

Patient characteristics
The dRTA evaluation was done after a mean period of 8.36 ± 0.99 weeks following the surgical intervention, and this period was not significantly different among the three groups.

Incomplete and complete dRTA were diagnosed in 17 (35%) and 9 (18%) children, respectively.

The characteristics of children with idRTA, complete dRTA and without dRTA are shown in Table 1. The study group included children at different ages due to varied referral indications. As compared with the children without dRTA, the idRTA group had an older age at surgery (P = 0.01), a longer duration of prior voiding symptoms (P = 0.003) and a higher prevalence of bilateral VUR (P = 0.02).


View this table:
[in this window]
[in a new window]

  		Table 1. Characteristics of the study group

 
The study patients had normal (≥90 ml/min/1.73 m2) eGFRs at the time of dRTA evaluation (Table 1). Before surgery, the mean eGFRs were ≥90 ml/min/1.73 m2 in the three groups; however, the individual eGFRs were <90 ml/min/1.73 m2 in two patients with complete dRTA (74 and 76 ml/min/1.73 m2), in one patient with idRTA (78.5 ml/min/1.73 m2) and in four patients with no dRTA (72, 74.2, 75.5, 84.2 ml/min/1.73 m2).

Fifty age- and gender-matched controls, with no renal issue, showed reference mean eGFR of 113.06 ± 9.61 ml/min/1.73 m2 (100.5–138).

Characteristics of dRTA
Nine patients with complete dRTA manifested basal hyperchloraemic metabolic acidosis, normal plasma anion gap and positive urine anion gap. Three of them (33%) had hypokalaemia, two (22%) had normokalaemia and four (45%) were hyperkalaemic. A TTKG below five in four hyperkalaemic patients suggested an inappropriately low potassium excretion. Complete dRTA was further sub-categorized. Hyperkalaemia and urine pH >5.5 suggested voltage-dependent dRTA in three patients, and urine pH <5.5 in one hyperkalaemic patient suggested reduced aldosterone bioactivity [2,21,22]. Hypokalaemia and urine pH >5.5 suggested secretory dRTA in three patients; while two patients had rate-limiting dRTA based on normal serum potassium levels and urine pH <5.5 [2]. None of these children manifested glucosuria, hypouricaemia or hypophosphataemia.

In the absence of a basal metabolic acidosis, idRTA evaluation was conducted in 40 children by ammonium chloride acidification test. Eight patients required repeat ammonium chloride administration; five due to an inability to tolerate the first dose and three due to an inadequate acidification with the first dose. Incomplete dRTA was diagnosed in 17 (42%) of the investigated children, based on their inability to lower urine pH <5.5 despite induced systemic metabolic acidosis. Children with idRTA and those without dRTA revealed normal serum electrolytes including potassium and chloride levels.

Clinical manifestations
As shown in Table 1, the idRTA group had a lower mean height SDS as compared with those without dRTA (–1.94 ± 0.41 vs –0.46 ± 0.28; P < 0.001); however, the difference did not reach a statistically significant level for short stature (height SDS below 2) (18% vs 0%; P = 0.06). When compared with the complete dRTA group, the idRTA group did manifest significantly higher mean height SDS (–1.94 ± 0.41 vs –5.31 ± 1.95; P = 0.002), and significantly lower prevalence of short stature (18% vs 78%; P = 0.001). Height SDS distribution among the three groups is shown in Figure 1. The mean weight SDS was significantly lower in the idRTA group as compared with those without dRTA (–0.73 ± 0.26 vs –0.08 ± 0.53; P < 0.001).


Figure 1
View larger version (8K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1. Median height SDS in the study group (P < 0.001 for incomplete vs no dRTA).

 
The age- and gender-matched controls, with no renal issue, showed a significantly higher corresponding height SDS (–0.39 ± 0.25 vs –1.94 ± 0.41; P < 0.001), and weight SDS (–0.03 ± 0.39 vs –0.73 ± 0.26; P < 0.001) as compared with the idRTA group. Similarly, the complete dRTA group manifested significantly lower height SDS (–5.31 ± 1.95 vs –0.35 ± 0.24; P < 0.001), and weight SDS (–3.9 ± 1.5 vs –0.04 ± 0.43; P < 0.001) as compared with the controls. However, the difference in height SDS (–0.46 ± 0.28 vs –0.50 ± 0.23; P = 0.30) and weight SDS (–0.08 ± 0.53 vs –0.06 ± 0.35; P = 0.83) was not significant between children without dRTA and the controls.

Nephrocalcinosis and rickets were not diagnosed in any patient with idRTA or no dRTA; however, the complete dRTA group manifested these clinical stigmata in 22% and 33% children, respectively.

Biochemical parameters
Despite an apparently normal acid–base profile (Table 1), the idRTA group had lower blood pH (P = 0.001) and serum bicarbonate levels (P = 0.04) as compared with no dRTA group; however, the difference was not significant for PCO2 (P = 0.12), serum calcium (P = 0.21) and serum phosphate (P = 0.39) levels.

Hypercalciuria was diagnosed in 78% of the children with complete dRTA compared with none with idRTA or without dRTA. Interestingly, despite urinary calcium to creatinine ratios being below the cut-offs for diagnosis of hypercalciuria [19,20], the idRTA group manifested higher ratios than the no dRTA group (P = 0.001). Fractional excretion of urinary sodium was high in all the three groups (Table 1); however, the difference among the groups was not significant (P = 0.41).

Factors associated with lower height SDS
On univariate analysis, height SDS was significantly associated with age at surgery (ß = –0.32; P = 0.02), duration of voiding symptoms (ß = –0.40; P = 0.004), bilateral VUR (ß = –0.43; P = 0.002) and presence of dRTA (ß = –0.88; P < 0.001). However, on multivariate analysis, the association was significant only between dRTA and the height SDS (Table 2).


View this table:
[in this window]
[in a new window]

  		Table 2. The association between the baseline characteristics and the height SDS scores

 
On correlation analysis, height SDS was associated with weight SDS (r = 0.93; P < 0.001), blood pH (r = 0.83; P < 0.001) and serum bicarbonate levels (r = 0.85; P = <0.001). The associations of height SDS with serum bicarbonate levels and with blood pH are shown in Figures 2 and 3, respectively.


Figure 2
View larger version (10K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2. The relationship between height SDS and serum bicarbonate levels in the study group.

 

Figure 3
View larger version (7K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3. The relationship between height SDS and blood pH in the study group.

 


   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
Acknowledgements
 References
 
Based on recently reported high prevalence of idRTA in adults with osteoporosis [9,10], our goal was to assess the effect of idRTA on height SDS in children. The study group was selected due to previously reported high prevalence of idRTA in children with obstructive uropathy [14,15].

The children with idRTA manifested significantly lower mean height SDS as compared with the PUV children without dRTA. The prevalence of short stature (height SDS below 2) was higher too in the idRTA group; but the difference did not turn out statistically significant. Age-matched controls showed higher height SDS as compared with the idRTA group. We did not come across a similar study involving children with idRTA; however, idRTA prevalence of 30% in adult patients with osteopenia [9] and 19% with osteoporosis [10] has been reported. Interestingly, Pongchaiyakul C et al., in their population-based study in Thailand, did not find higher osteoporosis prevalence in adults evaluated due to diagnosed primary idRTA [23]. Their results were similar to statistically non-significant short stature prevalence (height SDS below 2) in our idRTA group.

Despite a similar methodology for idRTA evaluation (short ammonium chloride acidification) in other studies [9,10,23] and ours, the difference in the observations could be due to different study designs. Weger et al. evaluated idRTA in the presence of already diagnosed osteoporosis [9,10]; while Pongchaiyakul C et al., similar to our study, assessed skeletal manifestation in adults with already diagnosed idRTA [23]. Unlike the Thai study, we picked a trend towards lower height SDS in our idRTA patients [23]. This difference in the observation can be attributed to a more substantial effect of idRTA in children, different skeletal parameters studied or to different aetiologies of idRTA in the two studies. Similar to the results from Weger et al., lower height SDS in our idRTA group supports the hypothesis that idRTA can affect skeletal parameters; however, other concomitant factors may affect severity of the observed clinical effect.

Despite absence of a basal metabolic acidosis, the clinical impact of idRTA can be explained by the renal acid–base handling. In response to a positive acid balance, normal renal acidification mechanisms can increase compensatory renal ammonium ion excretion to more than double [24]; however, a partial renal acidification defect, due to an idRTA, can induce recurrent positive acid loads at the times of increased protein load or intermittent catabolic stress [24,25]. Despite blood pH and serum HCO3 values being within the normal range in our patients with idRTA and without dRTA, a statistically significant difference in their absolute values signifies a tendency to develop metabolic acidosis in the presence of idRTA. Wager et al. observed a similar trend in bone mineral density scores in the presence of idRTA [10]. A strong correlation of height SDS with mean blood pH, and serum bicarbonate levels, suggests the mechanistic explanation for the lower height SDS in our patients. Furthermore, increased osteoblast and osteoclast activation is reported in the presence of idRTA [26]. In a nutshell, idRTA is a state of increased NH3, and thus NH4+ excretion, which leads to an alkaline urine and hypocitraturia in association with concomitant increased bone turnover [7].

In our study group, the patients from the idRTA and complete dRTA groups were significantly older as compared with those without dRTA. We examined the possible mechanisms that could affect height in our patients due to long-standing obstruction, independent dRTA. A confounding effect of long-standing renal insufficiency appears less likely in view of normal GFR values in the idRTA group prior to and following the surgery. Polyuria after the surgery can potentially affect growth due to recurrent dehydration episodes; however, dRTA evaluation shortly after the surgical intervention suggests a minimal effect due to excessive diuresis [27,28]. All the three groups had natriuresis at the time of evaluation; however, the difference was not statistically different enough to explain the difference in height SDS. Of note, use of height SDS, rather than absolute height, corrects for the variability in age as SDS scores are considered independent of age. A significant difference in height SDS between idRTA and the age-matched controls further supports the observation. Use of growth charts developed from a population similar to the study group for height SDS evaluation excludes confounding effect due to race or general nutritional status of the local population. A delay in PUV intervention has been previously associated with a higher prevalence of idRTA and complete dRTA [12]. Apparently, older age in our idRTA group contributed to lower height SDS through an increased prevalence of idRTA.

Systemic alkalinization does improve growth parameters in children with complete dRTA [5,6]. Alkali therapy in idRTA can prevent recurrent nephrolithiasis [7,8]; its effect on height SDS in idRTA is not defined. Sebastian et al. demonstrated an improvement in calcium and phosphorus balance, decrease in bone resorption, and increase in the rate of bone formation with oral administration of potassium bicarbonate in post-menopausal women despite no apparent acidification defect [29]. Based on these observations, diets rich in fruit or vegetables, or supplementation with potassium bicarbonate can reduce acid load and so improve bone status at the stage of idRTA. This issue needs evaluation in longitudinal studies.

The relevance of our findings in obstructive uropathy-associated idRTA to patients with primary idRTA can be debated. Obstructive uropathy induces renal injury through multiple mechanisms including increased tubular hydrostatic pressure, activated rennin–angiotensin axis, and through transforming growth factor ß-mediated interstitial injury [30]; dRTA, in turn, can be a result of direct tubulointerstitial injury with or without associated aldosterone resistance. In contrast, primary dRTA is usually a result of a specific renal tubular acidification defect [2–6]. As a result of a more generalized renal injury, obstructive uropathy can potentially induce more severe growth retardation through renal insufficiency, natriuresis and polyuria as compared with primary dRTA [31].

Despite a statistically compelling trend in the clinical manifestations, cross-sectional design is a limitation of the study. However, a detailed evaluation to exclude an alternative aetiology for short stature, a single aetiology for dRTA, and a reasonably sized study cohort adds strength to the observations. Although, we did not determine vitamin D status, a significant vitamin D deficiency appears less likely due to a practice of regular vitamin supplementation in younger children and, in general, a good exposure to sunshine in our study group. Serum parathyroid hormone (PTH) levels were not available in our patients; however, both Weger M. (despite osteoporosis) and Pongchaiyakul et al. found normal PTH levels in their study cohorts [9,23].

A statistically significant association between height SDS and idRTA in children is a novel observation. Further studies are needed to confirm a place for idRTA evaluation in children at a higher risk to develop idRTA and in the presence of an unexplained slow growth velocity.



   Acknowledgements
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgements
References
 
The authors are greatful to Dr. Brian Steele and Dr. Narayan Prasad for the inputs on the manuscript.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgements
 References
 

  1. Wrong O, Davies HEF. The excretion of acid in renal disease. Q J Med (1959) 28:259–313.[Web of Science][Medline]
  2. Rodriguez Soriano J. Renal tubular acidosis: the clinical entity. J Am Soc Nephrol (2002) 13:2160–2170.[Free Full Text]
  3. Brenner RJ, Spring DB, Sebastian A, et al. Incidence of radiographically evident bone disease, nephrocalcinosis, and nephrolithiasis in various types of renal tubular acidosis. N Engl J Med (1982) 307:217–221.[Abstract]
  4. Caruana RJ, Buckalew VM Jr. The syndrome of distal (type 1) renal tubular acidosis. Clinical and laboratory findings in 58 cases. Medicine (1988) 67:84–99.[Medline]
  5. Bajpai A, Bagga A, Hari P, Bardia A, Mantan M. Long-term outcome in children with primary distal renal tubular acidosis. Indian Pediatr (2005) 42:321–328.[Web of Science][Medline]
  6. Caldas A, Broyer M, Dechaux M, Kleinknecht C. Primary distal tubular acidosis in childhood: clinical study and long-term follow-up of 28 patients. J Pediatr (1992) 121:233–241.[CrossRef][Web of Science][Medline]
  7. Osther PJ, Bollerslev J, Hansen AB, Engel K, Kildeberg P. Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium, bone and citrate metabolism. Urol Res (1993) 21:169–173.[CrossRef][Web of Science][Medline]
  8. Konnak JW, Kogan BA, Lau K. Renal calculi associated with incomplete distal renal tubular acidosis. J Urol (1982) 128:900–902.[Web of Science][Medline]
  9. Weger W, Kotanko P, Weger M, Deutschmann H, Skrabal F. Prevalence and characterization of renal tubular acidosis in patients with osteopenia and osteoporosis and in non-porotic controls. Nephrol Dial Transplant (2000) 15:975–980.[Abstract/Free Full Text]
  10. Weger M, Deutschmann H, Weger W, Kotanko P, Skrabal F. Incomplete renal tubular acidosis in ‘primary’ osteoporosis. Osteoporosis Int (1999) 10:325–329.[CrossRef][Web of Science][Medline]
  11. Sharma RK, Sharma AP, Kapoor R, Gupta A. Prognostic significance of distal renal tubular acidosis in posterior urethral valve. Pediatr Nephrol (2001) 16:581–585.[CrossRef][Web of Science][Medline]
  12. Sharma RK, Sharma AP, Kapoor R, Pandey CM, Gupta A. Prognostic factors for persistent distal renal tubular acidosis after surgery for posterior urethral valves. Am J Kidney Dis (2001) 38:488–493.[Web of Science][Medline]
  13. Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children and adolescents. Pediatric Clinics of North America (1987) 34:571–590.[Web of Science][Medline]
  14. Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM, Tamminen-Mobius TE. International system of radiographic grading of vesicoureteric reflux. International reflux study in children. Pediatr Radiol (1985) 15:105–109.[CrossRef][Web of Science][Medline]
  15. Batlle DC, Hizon N, Cohen E, Gutterman C, Gupta R. The use of the urinary anion gap in diagnosis of hyperchloraemic metabolic acidosis. N Engl J Med (1988) 318:594–599.[Abstract]
  16. Rodriguez-Soriano J. Renal tubular acidosis. In: Pediatric Kidney Diseases—Edelmann CM, Bernstein J, Meadow SR, Spitzer A, Travis L, eds. (1992) Boston: Little, Brown and Co. ; 1737–1776.
  17. Agarwal DK, Agarwal KN, Upadhyay SK, Mittal R, Prakash R, Rai S. Physical and sexual growth pattern of affluent Indian children from 5 to 18 years of age. Indian Pediatr (1992) 29:1203–1268.[Medline]
  18. Agarwal DK, Agarwal KN. Physical growth of Indian affluent children (Birth–6 years). Indian Pediatr (1994) 31:377–413.[Medline]
  19. Ghazali S, Barratt TM. Urinary excretion of calcium and magnesium in children. Arch Dis Child (1974) 49:97–101.[Abstract/Free Full Text]
  20. Sweid HA, Bagga A, Vaswani M, et al. Urinary excretion of minerals, oxalate and uric acid in north Indian children. Peidatr Nephrol (1997) 11:189–192.[CrossRef]
  21. Rodriguez-Soriano J, Ubetagoyena M, Vallo A. Transtubular potassium concentration gradient: a useful test to estimate renal aldosterone bio-activity in infants and children. Pediatr Nephrol (1990) 4:105–110.[CrossRef][Web of Science][Medline]
  22. Schwarz C, Benesch T, Kodras K, Oberbauer R, Haas M. Complete renal tubular acidosis late after kidney transplantation. Nephrol Dial Transplant (2006) 21:2615–2620.[Abstract/Free Full Text]
  23. Pongchaiyakul C, Domrongkitchaiporn S, Stitchantrakul W, Chailurkit La-or, Rajatanavin R. Incomplete renal tubular acidosis and bone mineral density: a population survey in an area of endemic renal tubular acidosis. Nephrol Dial Transplant (2004) 19:3029–3033.[Abstract/Free Full Text]
  24. Alpren RJ, Sakhaee K. The clinical spectrum of chronic metabolic acidosis. Homeostatic mechanisms produce significant morbidity. Am J Kidney Dis (1997) 29:291–302.[Web of Science][Medline]
  25. Barzel US, Massey LK. Excess dietary protein can adversely affect bone. J Nutr (1998) 128:1051–1053.[Abstract/Free Full Text]
  26. Green J, Kleeman CR. Role of bone in regulation of systemic acid–base balance. Kidney Int (1991) 39:9–26.[Web of Science][Medline]
  27. van Lieburg AF, Knoers NV, Monnens LA. Clinical presentation and follow-up of 30 patients with congenital nephrogenic diabetes insipidus. J Am Soc Nephrol (1999) 10:1958–1964.[Abstract/Free Full Text]
  28. Naghizadeh S, Kefi A, Dogan HS, Burgu B, Akdogan B, Tekgul S. Effectiveness of oral desmopressin therapy in posterior urethral valve patients with polyuria and detection of factors affecting the therapy. Eur Urol (2005) 48:819–825.[CrossRef][Web of Science][Medline]
  29. Sebastin A, Harris ST, Ottaway JH, Todd KM, Morris RC Jr. Improved mineral balance and skeletal metabolism in post-menopausal women treated with potassium bicarbonate. N Engl J Med (1994) 330:1776–1781.[Abstract/Free Full Text]
  30. Roth KS, Koo HP, Spottswood SE, Chan JC. Obstructive uropathy: an important cause of chronic renal failure in children. Clin Pediatr (2002) 41:309–314.[Abstract/Free Full Text]
  31. Shi Y, Li C, Thomsen K, et al. Neonatal ureteral obstruction alters expression of renal sodium transporters and aquaporin water channels. Kidney Int (2004) 66:203–215.[CrossRef][Web of Science][Medline]
Received for publication: 22. 1.07
Accepted in revised form: 24. 4.07


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
22/10/2879    most recent
gfm307v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Sharma, A. P.
Right arrow Articles by Filler, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sharma, A. P.
Right arrow Articles by Filler, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?