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NDT Advance Access published online on October 19, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm698
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Renal Magnesium Wasting And Tubular Dysfunction in Leptospirosis

Sookkasem Khositseth1, Niwatchai Sudjaritjan2, Paiboon Tananchai3, Sompong Ong-ajyuth4, Visith Sitprija5 and Visith Thongboonkerd6

1 Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathumthani, Thailand 2 Department of Medicine 3 Department of Clinical Pathology, Nan Hospital, Nan, Thailand 4 Department of Biochemistry, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand 5 Queen Saovabha Memorial Institute, Bangkok, Thailand 6 Medical Molecular Biology Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

Correspondence and offprint requests to: Correspondence and offprint requests to: Visith Thongboonkerd Medical Molecular Biology Unit, Office for Research and Development, 12th Floor Adulyadej Vikrom Building, Siriraj Hospital, 2 Pronnok Road, Bangkok 10700, Thailand. Phone/Fax: +66-2-4184793; E-mail: thongboonkerd{at}dr.com (or) vthongbo{at}yahoo.com



   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 Conclusions
 References
 
Background. Tubulo-interstitial nephritis is the main cause of acute renal injury in leptospirosis. The aim of this study was to evaluate renal tubular function and excretion of solutes in leptospirosis patients during a recent outbreak of leptospirosis in Nan province, Thailand.

Methods. Clinical manifestations were recorded and routine laboratory tests were performed upon admission. Renal tubular functions including tubular reabsorption of phosphate (TRP), fractional excretion of magnesium (FEMg), urinary calcium to creatinine ratio (Uca/cr), urine N-acetyl-ß-D glucosaminidase (NAG) and urine ß2-microglobulin were serially monitored during 2 weeks after admission.

Results. A total of 20 leptospirosis patients were recruited. Nine (45%) patients had acute renal failure (ARF). Increased urine NAG and ß2-microglobulin, which indicate proximal tubular dysfunction, were demonstrated in all 20 (100%) patients. Fifteen (75%) patients had hypermagnesuria, whereas 10 (50%) patients had decreased TRP. Renal magnesium (Mg) and phosphate (P) wasting caused hypomagnesaemia and hypophosphataemia in nine and three patients with ARF, respectively. These abnormal findings significantly improved within 2 weeks after admission.

Conclusions. We conclude that renal Mg and P wasting commonly occur in patients with leptospirosis. The measurement of Mg and P levels in both serum and urine of leptospirosis patients, especially those with ARF, is therefore highly recommended.

Keywords: leptospirosis; magnesium; nephropathy; renal failure; tubular dysfunction



   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 Conclusions
 References
 
Leptospirosis is a common zoonosis caused by Leptospira interrogans. Although this disease is seen worldwide, it is more common in the tropics [1]. The clinical syndrome of leptospirosis varies from subclinical infection and self-limited anicteric febrile illness to life-threatening disease. Renal involvement is a prominent feature of both mild and severe forms of leptospirosis [2]. Acute renal failure (ARF) is observed in 17.9–80% of the patients with leptospirosis, depending upon the severity of the disease and the criteria for diagnosis of ARF [2–6]. Tubulo-interstitial nephritis is the main cause of acute renal injury in leptospirosis [7]. There are several reports of renal tubular dysfunction in patients with leptospirosis [2,8–15]. The proximal tubule is the common site affected by leptospiral infection in both humans and animal models [16–18]. Although less common, dysfunction of the thick ascending limb of Henle's loop (TALH) has also been reported [11,14,19]. Magnesium (Mg), the second most abundant intracellular cation, is reabsorbed mainly at TALH. Therefore, any disturbance of function of tubular epithelial cells, especially at TALH, would affect tubular Mg reabsorption. However, the information on renal Mg handling in leptospirosis has not been available in the past. Herein, we report for the first time renal Mg wasting and serial dynamic changes in renal tubular functions in patients with leptospirosis during a recent outbreak in Nan, a province of northern Thailand. Previous reports on leptospirosis-associated renal tubular dysfunctions are also discussed.



   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 Conclusions
 References
 
Patients
We prospectively studied 20 patients with leptospirosis admitted in a secondary hospital at Nan province of Thailand during a recent outbreak of leptospirosis associated with the flooding disaster in September 2006. Among these patients, 15 were males, whereas five were females. The mean (±SD) age was 38.6 ± 15.5 years (range: 16–68 years). Written informed consents were obtained from all the patients. This study was approved by the Ethics Committee of Nan Hospital, Nan province, Thailand.

Diagnosis
The diagnostic tests for leptospirosis used in the present study included microagglutination test (MAT), indirect immunofluorescence antibody test (IFAT) and microcapsule agglutination test (MCAT). Panels of leptospiral serovars, including Australis, Sejroe, Grippotyphosa, Javanical and Louisiana were used for MAT. A definite serologic diagnosis of leptospirosis was defined using the following criteria [20–22]: (i)>4-fold (or >1:200) MAT titer (n = 11); (ii) ≥1:200 specific IgG or IgM titer as determined by the IFAT (n = 7) or (iii) positive leptospiral DNA as detected by the PCR assay (n = 2).

Initial investigations
History and findings from physical examination of these patients were recorded. All patients were clinically evaluated for dehydration, whereas central venous pressure (CVP) was monitored only in patients with low blood pressure. Initial investigations performed upon admission included complete blood count, hemoculture for detection of common aerobic bacteria and urinalysis. Serum electrolytes, blood urea nitrogen (BUN), serum creatinine (Cr), Ca, Mg, P, liver function test, lactate dehydrogenase (LDH), creatine kinase (CK) and glucose were measured using Olympus AU 400 Chemistry Analyser (Olympus, Philadelphia, USA). Serum anion gap (AG) was calculated using the formula: AG = [Na] – ([Cl] + [HCO3]).

Serial analysis of renal function
First-voided morning urine and blood samples were collected on days 1, 2, 5 and 14 after admission. Urine protein, Cr, Ca, Mg and P were measured by Olympus AU 400 Chemistry Analyser (Olympus, Philadelphia, USA) and urine sugar was analysed by Labstix (Bayer Diagnostics, Ontario, Canada). Urine N-acetyl-ß-D glucosaminidase (NAG) was measured using a spectrophotometric method [23], whereas urine ß2-microglobulin was measured by an enzyme-linked immunosorbent assay [24]. Blood samples were analysed for BUN, serum Cr, Ca, Mg and P. Urinary protein/creatinine ratio (Uprotein/cr), urinary calcium/creatinine ratio (Uca/cr), tubular reabsorption of phosphate (TRP) and fractional excretion of magnesium (FEMg) were calculated. Normal values of these parameters in adults are as follows: Uprotein/cr < 0.2 mg/mg (<0.02 g/mol), Uca/cr < 2 mg/mg (<0.7 mmol/mmol), TRP > 85% and FEMg < 2.2% [25,26]. The normal level of urine NAG for Thais is 0.42 ± 0.2 U/µmol creatinine (3.75 ± 1.83 U/g creatinine) [27]. Normal level of urine ß2-microglobulin for Thais is 45.9–31.5 g/mol creatinine (407 ± 279 µg/g creatinine) [28]. Estimated creatinine clearance (Ccr) was calculated using the Cockcroft–Gault equation [29]. ARF was defined as Ccr < 1.0 mL/s (60 mL/min) or serum Cr > 141.4 µmol/L (1.6 mg/dL) associated with recovery of renal function. Hyponatraemia, hypokalaemia, hypophosphataemia, hypocalcaemia and hypomagnesaemia were defined as serum Na < 130 mmol/L (130 mEq/L), K < 3 mmol/L (3 mEq/L), P < 0.8 mmol/L (2.5 mg/dL), Ca < 2.0 mmol/L (8 mg/dL) and Mg < 0.7 mmol/L (1.7 mg/dL), respectively. Hepatic involvement was defined as a serum aspartate aminotransferase (AST) >40 U/L, alkaline phosphatase (AP) > 104 U/L or total bilirubin > 17.1 µmol/L (1.0 mg/dL). Muscle involvement was defined as CK > 170 U.

Statistical analyses
Data are expressed as median and range, unless indicated otherwise. Statistical analyses were performed using the Mann–Whitney test, the Wilcoxon signed ranks test and the Spearman rank correlation coefficient. All computations were performed using the SPSS software package for Windows, version 14.0 (SPSS, Chicago, IL). P value ≤ 0.05 was considered statistically significant.



   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 Conclusions
 References
 
Clinical manifestations
Patient characteristics and clinical manifestations are summarized in Table 1. All patients presented with fever and myalgia for an average of 3 days prior to admission. Four patients had received initial fluid resuscitation from a primary hospital prior to referring. All 20 patients had dehydration as demonstrated by dry lips and buccal mucosa, poor skin turgor and/or sunken eyeballs. Nine (45%) patients had hypovolemic shock (mean arterial pressure < 70 mmHg and CVP < 8 cm H2O) and oliguric ARF on admission. Among these nine ARF patients, three received a single dose of furosemide (0.6—1 mg/kg/day) after adequate fluid resuscitation. The indication of furosemide administration was oliguria despite normal CVP. Four (20%) patients had jaundice. One (5%) patient had Weil's disease (serious icteric leptospirosis with thrombocytopaenia and hepatic and renal involvements). All patients had received oral doxycyclin at a dosage of 200 mg twice daily for 7 days in combination with intravenous injection of penicillin G sodium (1.5–2-million U every 6 h) or ceftriaxone (2 g per day) for 5–7 days. After such a therapy, the febrile illness recovered completely.


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  		Table 1. Patient characteristics and clinical manifestations (total n = 20)

 
Abnormal laboratory findings on admission date
Initial laboratory findings of all patients are shown in Table 2, whereas Table 3 summarizes number (and percentage) of patients who had abnormal initial laboratory findings. Microscopic and gross haematuria were detected in 45% of the cases. Glycosuria was detected in only one patient (5%) who had Weil's disease. Four patients (20%) had hypokalaemia, metabolic acidosis and hypophosphataemia. Of these four patients, three had normal anion gap metabolic acidosis without diarrhoea. Hyponatraemia was found in 30% of the cases. Hypocalcaemia was detected in five (25%) patients. Interestingly, hypomagnesaemia was found in 10 (50%) patients. Nine of these 10 hypomagnesaemic patients also had ARF.


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  		Table 2. Initial laboratory findings (n = 20)

 

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  		Table 3. Number of patients with abnormal initial laboratory findings (total n = 20)

 
Blood and urine cultures were negative for aerobic bacteria in all the patients. Non-renal involvements of leptospirosis in our series included liver injury (n = 8), muscle injury (n = 5), thrombocytopaenia (n = 7) and leucopaenia (n = 1). Elevated LDH and CK levels were normalized within 2 weeks in all the patients, whereas hepatic involvement recovered in all patients within 1 month after the onset of the disease (data not shown).

Serial monitoring of laboratory tests in patients with abnormal renal functions
After appropriate therapy, serial monitoring of Ccr and several urinary parameters that reflect renal tubular functions showed gradual improvement of Ccr (GFR) and tubular functions in patients who initially had abnormal renal functions (Table 4). Nine (45%) patients had hypovolaemic shock and oliguric ARF on admission with a median Ccr of 0.4 mL/s (25 mL/min). The median Ccr of these patients significantly increased to 1.1 mL/s (66 mL/min) 2 weeks later (P = 0.04, Table 4). Six (30%) patients had tubular proteinuria. Their median Uprotein/cr, ratio significantly declined from 0.08 to 0.01 g/mol within 2 weeks (P = 0.03, Table 4). Most patients had normal Uca/cr. Median Uca/cr on days 1, 2, 5 and 14 were 0.2, 0.3, 0.3 and 0.3 mmol/mmol, respectively. Ten (50%) patients had decreased TRP with a median of 77.9%, which significantly improved to 85% within 2 weeks (P = 0.005, Table 4). Of these 10 patients, five had ARF. Three patients who had low TRP and ARF developed hypophosphataemia, implicating that renal P wasting caused hypophosphataemia in these patients. Fifteen (75%) patients had hypermagnesuria. The median of their FEMg was 9.7% on day 1 and was significantly improved to 4.1% within 2 weeks (P = 0.02, Table 4). The FEMg was markedly elevated in nine hypomagnesaemic patients who developed ARF, indicating that renal Mg wasting caused hypomagnesaemia in these patients. There was a correlation between serum Mg levels and estimated Ccr (rs = 0.7, P < 0.01), and a reverse correlation between FEMg and estimated Ccr (rs = –0.5, P = 0.03). Among 15 patients with hypermagnesuria, three ARF patients who received furosemide had the FEMg of 18.3% and 9.8% on days 1 and 5, respectively. These were significantly higher than those of the other 12 patients without furosemide administration (their FEMg was 8.8% and 3.4% on days 1 and 5, respectively) (P < 0.05).


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  		Table 4. Serial monitoring of laboratory tests in patients with abnormal renal function

 
All the 20 patients (100%) had abnormal increased levels of urine NAG and urine ß2-microglobulin when compared to the normal levels of Thais [27,28]. The median level of urine NAG was 1.0 U/µmol (10.1 U/g creatinine) on day 1 and was significantly decreased to 0.6 U/µmol (5.4 U/g creatinine) within 2 weeks (P = 0.04, Table 4). Similarly, the median level of urine ß2-microglobulin was 273 g/mol creatinine (2417-µg/g creatinine) on day 1 and significantly declined to 13.2 g/mol creatinine (117 µg/g creatinine) within 2 weeks (P = 0.04, Table 4). Ccr (GFR), Uprotein/cr, Uca/cr, TRP and FEMg in patients who initially had normal levels of these tests and were not included into Table 4 remained persistently normal during these 2 weeks of observation.

Two patients had a history of hypertension with normal electrocardiogram upon admission and normal kidney size (by ultrasound). The first patient was a 68-year-old, 58-kg-weight man who had a history of hypertension for 20 years with a transient ischemic attack. His Uprotein/cr ratio declined from 0.02 g/mol upon admission to 0.01 g/mol 2 months after the admission. His serum Cr also declined gradually, from 150 µmol/L upon admission to 141, 124 and 106 µmol/L at 2 weeks, 2 months and 10 months after the admission, respectively. However, the calculated Ccr was persistantly lower than 1.0 mL/s until 10 months later. The estimated Ccr was 0.55, 0.59, 0.68 and 0.79 mL/s upon admission, 2 weeks, 2 months and 10 months after the admission, respectively.

The second patient was a 62-year-old, 38-kg-weight woman with a history of hypertension for 1 year. Her Uprotein/cr ratios were 0.02 and 0.01 g/mol upon admission and 10 months after the admission, respectively. Her serum Cr also declined gradually, from 88.4 µmol/L upon admission to 79.6 and 70.7 µmol/L at 2 and 10 months after the admission, respectively. Notably, her serum Cr levels were within normal range since admission until 10 months later. However, the estimated Ccr were lower than the normal limit (1.0 mL/s) since admission until 10 months later. The estimated Ccr was 0.47, 0.52 and 0.58 mL/s upon admission, 2 months and 10 months after the admission, respectively. The discrepancy between serum Cr levels and estimated Ccr in these two patients might be due to their low body weights, while their ages were high, leading to the low estimated Cr using the Cockcroft–Gault equation [29].

Laboratory findings in patients with ARF versus those without ARF
A total of nine patients (45%) developed ARF as a serious renal complication of leptospirosis. Urinary parameters of patients with and without ARF were compared and are shown in Table 5. The nine patients with ARF had significantly lower TRP than those without ARF (median TRP was 71.9 vs. 84%, respectively, P = 0.02). In contrast, FEMg was significantly greater in these ARF patients (10.1 vs. 3.1% in ARF vs. non-ARF patients, respectively, P < 0.01). Uca/cr and Uprotein/cr were comparable between the two groups. In addition to these urinary parameters, platelet counts of patients with ARF were significantly lower than those of patients without ARF (Table 5).


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  		Table 5. Laboratory findings in patients with ARF versus those without ARF

 


   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
Conclusions
 References
 
We present herein clinical manifestations, laboratory data and renal tubular dysfunctions in a group of patients with leptospirosis during a recent outbreak in Thailand. The clinical manifestations of leptospirosis patients and abnormalities of routine laboratory tests observed in our present study were consistent with those previously reported in other large series [6,30]. The findings from urinalysis of our patients were consistent with several previous reports on haematuria and proteinuria occurring during the early phase of leptospirosis [2,6]. ARF is a common renal complication in leptospirosis. The incidence of leptospirosis-induced ARF depends upon the criteria for diagnosis. Using the same criteria, our incidence of 45% of leptospirosis-induced ARF is slightly less than the incidence of 54% reported by Katz et al. [6]. Similar to previous studies, we found that hypovolemia is a prominent finding in leptospirosis-induced ARF [31].

To the best of our knowledge, this is the first study reporting renal Mg wasting in most (75%) of the patients with leptospirosis. We also described increasing levels of urine NAG and urine ß2-microglobulin, which indicate tubular damage in all (100%) the patients. Hypermagnesaeria and hyperphosphataeria were the two most common tubular dysfunctions (found in 75 and 50% of cases, respectively), which mostly presented in patients with ARF but also occurred in patients without ARF. However, we found that ARF aggravated these two common complications, leading to hypomagnesaemia and hypophosphataemia. Moreover, our present study has been the first to demonstrate the correlation between serum Mg and estimated Ccr, and the reverse correlation between FEMg and estimated Ccr in leptospirosis patients.

Normally, only 3% of filtered Mg is excreted into the urine. The major site of Mg reabsorption in the kidney is TALH, where 65–70% of the filtered Mg can be reabsorbed [32]. Renal Mg reabsorption can be inhibited by several conditions including hypermagnesaemia, hypervolaemia, loop diuretics and stimulation of the calcium-sensing receptor by hypercalcaemia. Hypermagnesaemia, hypervolaemia and hypercalcaemia were not detected in our patients. Although a single dose of furosemide administration could be a cause of hypermagesuria in three patients, renal magnesium wasting was consistently detected in the remaining 12 patients without furosemide administration. Thus, TALH dysfunction seemed to be the most likely cause of hypermagnesuria in our case series. There are only few reports of TALH dysfunction in leptospirosis patients [11,14,19] (Table 6). These studies described an abnormal response of TALH to a furosemide test, indicating the reduced activity of apical Na+-K+-2Cl– cotransporter in leptospirosis patients with hypokalemic metabolic alkalosis [11,14,19]. However, none of these reports has discussed Mg status or renal Mg handling in their patients. We report herein that renal Mg wasting is a major renal complication in leptospirosis patients.


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  		Table 6. Previous reports on leptospirosis-induced renal tubular dysfunction

 
Interestingly, we did not observe hypokalaemic metabolic alkalosis in our patients with renal Mg wasting. Therefore, the abnormalities of apical Na+-K+-2Cl– cotransporter, apical K+ channel and basolateral Cl– channel at TALH, which are the common causes of hypokalemic metabolic alkalosis and hypermagnesuria in Bartter's syndrome, could not explain our patients’ biochemical data. Hypermagnesuria in our patients might be a result of other mechanisms. One possibility is that, perhaps, leptospirae may cause direct damage to paracellin-1, a renal tight junction protein required for paracellular Mg reabsorption in TALH. Further investigations to elucidate the molecular mechanisms of hypermagnesuria, which leads to hypomagenesaemia in leptospirosis patients, would be a significant advance to better understand the abnormal renal Mg handling in leptospirosis.

Several reports have described renal tubular dysfunctions in leptospirosis patients (Table 6) [2,8–12,14]. Proximal tubular dysfunction seems to be the most prevalent form of renal tubular disorders in leptospirosis, as demonstrated by hyperphosphaturia, glycosuria and proximal renal tubular acidosis in several studies [2,10,12–14]. The high prevalence of proximal tubular dysfunction may be simply explained by the fact that the proximal tubule is one of the major targets for leptospiral colonization [33]. As the increased urine NAG and ß2-microglobulin are the highly specific markers for proximal tubular disease [34], the high urinary levels of these two markers in all of our patients have clearly confirmed that proximal renal tubular cells are damaged in leptospirosis patients.

Liberopoulos et al. [12] have reported hyperphosphaturia and glycosuria in a leptospirosis patient with severe hyperbilirubinaemia but without ARF. Our finding of proximal renal tubular dysfunction, as indicated by hyperphosphaturia in leptospirosis patients without ARF, supports the study in guinea pigs by Magladi et al. [17], demonstrating that functional alterations in tubular cells precede a drop in the GFR. Hyperphosphaturia in our patients had resolved within 2 weeks, the duration of which was shorter than the 40 days reported by Liberopoulos et al. [12]. Incomplete and complete proximal renal tubular acidosis have been reported in a total of 13 leptospirosis patients [2,10,13,14]. These findings are consistent with a recent study by Andrade et al. [16], which shows the reduction of sodium/hydrogen exchange isoform 3 (NHE3) in leptospire-infected hamsters.

The incidence of 20% of hypokalaemia in our present study was comparable to that of 18% reported by Ko et al. [30]. However, in other series, 26–45% incidence of hypokalaemia caused by kaliuresis has been reported [2,8,9,35]. Molecular mechanisms of hypokalaemia in leptospirosis patients can well be explained by two studies [14,16]. The first study by Wu et al. [14] has demonstrated the inhibition of activity and mRNA expression of Na+-K+-2Cl– cotransporter in medullary thick ascending limb cells by outer membrane protein extracted from Leptospira shermani. The second study by Andrade et al.[16] has demonstrated the down-regulation of NHE3 at the proximal tubule, whereas expression of {alpha}-ENaC and {alpha}-Na+-K+-ATPase in the renal cortex remained unchanged. Interestingly, urinary calcium excretion was normal in our patients. This finding supports the normal activity of thiazide-sensitive Na+-Cl– cotransporter in leptospire-infected hamsters studied by Andrade et al. [16]. In addition to the aforementioned references, the pathogenic mechanisms of leptospirosis-induced renal tubular dysfunction have been extensively investigated by several investigators during the last decade [16,18,36–39].

Differential diagnosis of our patients needs a discussion. Another disease that may mimic clinical manifestations and laboratory findings of leptospirosis is hantavirus infection. These two infectious diseases have several common features, including flu-like symptoms, conjunctivitis, hemorrhage, haematuria, proteinuria and ARF [40]. Dual infection with both leptospire and hantavirus has been reported [41]. Thus, the seropositivity for leptospirosis does not exclude a simultaneous hantaviral infection. However, hantaviral infection is uncommon in Thailand [42].

A limitation of this study should also be noted. We did not measure urinary fractional excretion of HCO3 (FEHCO3) and did not monitor urinary pH. Therefore, acidification defect was not completely investigated in our patients. However, without evidence of extrarenal loss of HCO3, renal tubular acidosis was suspected in our two patients with normal anion gap metabolic acidosis. We also did not measure urinary Na and K before administration of intravenous fluid. Therefore, we cannot report renal Na and K losses in more detail, as described previously [2,8,12].



   Conclusions
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusions
References
 
Renal tubular dysfunction is a common complication of leptospirosis. In addition to the well-known tubular dysfunctions, hypermagnesuria and hyperphosphaturia, which can lead to hypomagnesaemia and hypophosphataemia, respectively, are also common in leptospirosis. These two common tubular disorders should be emphasized during management of leptospirosis. We, therefore, recommend monitoring Mg and P levels in serum and urine of leptospirosis patients, especially those with ARF.



   Acknowledgments
 
We thank all nursing staff at Nan Hospital for their assistance with specimen collection and are grateful to Supin Natungkam and Sompong Liammongkolkul for their technical assistance. This work was supported by the Thammasat University Research Development fund (to S.K.). V.T. is supported by The Thailand Research Fund, Commission on Higher Education, the National Center for Genetic Engineering and Biotechnology, Mahidol University, and by the National Research Council of Thailand.

Conflict of interest statement. There is no conflict of interest in this study.

ARF, acute renal failure; BUN, blood urea nitrogen; CK, creatine kinase; FEMg, fractional excretion of magnesium; IFAT, indirect immunofluorescence antibody test; LDH, lactate dehydrogenase; MAT, microagglutination test; MCAT, microcapsule agglutination test; NAG, N-acetyl-ß-D glucosaminidase; TALH, thick ascending limb of Henle's loop; TRP, tubular reabsorption of phosphate; Uca/cr, urine calcium/creatinine ratio; Uprotein/crurine protein/creatinine ratio.



   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusions
 References
 

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Received for publication: 13. 5.07
Accepted in revised form: 10. 9.07


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