Mehmet Bakkaloglu

A study of the etiology of idiopathic calcium urolithiasis in children : Hypocitruria is the most important risk factor

PURPOSE To determine the association of metabolic risk factors with pediatric calcium urolithiasis we compared metabolic evaluation data on children with idiopathic calcium stones and those on healthy children. MATERIALS AND METHODS Metabolic evaluation was done in 78 calcium stone formers 1 to 15 years old (mean age 7.2) who were free of urinary tract infection, anatomical abnormalities, and metabolic, endocrinological and intestinal disorders, and in 24 healthy children. Evaluation included serum biochemistry, and measurement of daily excretion of urinary calcium, oxalate, urate, phosphorus, citrate and magnesium. RESULTS Demographic characteristics, serum parameters, and daily excretion of calcium, urate, phosphorus and magnesium did not differ statistically in the 2 groups. However, urinary oxalate was significantly higher and urinary citrate was significantly lower in stone formers than in controls (p = 0.002 and 0.028, respectively). Hypocitruria and hyperoxaluria were 4.3 and 3-fold more common in stone formers than in controls, respectively. Multivariate analysis using logistic regression showed that hypocitruria was the only significant risk factor for idiopathic calcium stones (p = 0.008). CONCLUSIONS Hypocitruria was the most important risk factor in our patients. Hyperoxaluria was also common and accompanied hypocitruria in many stone formers. In contrast to many previous reports, we failed to show that hypercalciuria is an important metabolic defect for idiopathic calcium stones, possibly because our study evaluated a different population.

Prospective long-term followup of patients with asymptomatic lower pole caliceal stones.

PURPOSE The intervention time of asymptomatic lower pole calculi remains controversial. In this prospective study we evaluated the natural history and progression rate of asymptomatic lower pole stones. MATERIALS AND METHODS Patients were followed every 6 months. Computerized tomography in even years, ultrasound scan in odd years after initial visit and abdominal plain films between these visits were evaluated. The largest diameter was measured for each calculus and the cumulative diameter was calculated for cases of multiple stones. Disease progression was defined as pain experienced during followup, stone growth or the need for intervention. RESULTS A total of 24 patients, 14 male and 10 female, were followed for a mean of 52.3 months (range 24 to 72). Of the 24 patients 3 had bilateral lower pole stones. Mean cumulative stone diameter at presentation was 8.8 mm (range 2.0 to 26.0). Progression in stone size was demonstrated in 9 of 27 renal units (33.3%) with 2 (11.1%) requiring intervention. There was no need for intervention during the first 2 years of followup. Three stones passed spontaneously without any symptoms. Pain developed in 3 patients during followup, and 2 of them passed a stone and responded to the analgesics without further treatment. None of the patients had a pyelonephritic attack during followup. CONCLUSIONS Our results showed that observation could be considered for patients with asymptomatic lower pole stones. However, patients should be counseled about the 33% disease progression and 11% intervention rates.

Percutaneous nephrolithotomy in patients aged 60 years or older.

PURPOSE To assess the safety and efficacy of percutaneous nephrolithotomy in patients more than 60 years old. PATIENTS AND METHODS We retrospectively evaluated and compared the data of 28 percutaneous nephrolithotomies (PCNL) performed on 27 patients aged 60 years and older (mean 65.8) with the data of the remaining 178 PCNL procedures on 166 patients performed in our clinic between December 1997 and December 1999. RESULTS Although staghorn stones seemed to be more common in the elderly group (25% v 22%), no statistical significance was demonstrated (P = 0.715), and the stone burden was similar for the two groups (P = 0.112). The only interesting finding in terms of patient characteristics was a significantly higher incidence of solitary kidney in patients aged 60 years or older (29% v 7%; P = 0.003). The success rates (stone-free patients and patients with residual stones <4 mm) were similar, being 89% for the elderly group and 92% for the younger patients (P = 0.718). Transfusion rates were also similar (21.4% in the elderly v 18% in the younger group; P = 0.662). No significant complication was observed in this elderly group, and no renal deterioration has been detected even in the follow-up of patients with a solitary kidney. CONCLUSIONS Despite the somewhat higher stone burden in the elderly patients (1077.92 mm2 v 920.85 mm2), the stone-free rate was similar to that obtained in the younger patients, without any higher rates of complications or blood transfusions or longer hospital stay. Percutaneous nephrolithotomy is a safe and effective method of stone treatment in the elderly, even if they have a solitary kidney or complex calculi.

Oral Potassium Citrate Treatment for Idiopathic Hypocitruria in Children With Calcium Urolithiasis

PURPOSE We evaluated the clinical and laboratory outcome of oral potassium citrate treatment in children with idiopathic hypocitruria and calcium stones. MATERIALS AND METHODS The charts of 64 children 1 to 15 years old with hypocitruria and calcium stones (median age 7.2) treated with oral potassium citrate were reviewed. Evaluation parameters were tolerability, adverse reactions, metabolic profile and stone recurrence. RESULTS No serious adverse reaction due to potassium citrate administration was recorded. Normal citrate excretion was restored in all patients. After treatment median urinary citrate daily plus or minus SD increased from 197 +/- 72 to 632 +/- 218 mg./1.73 m.2 (p <0.001) and mean urinary pH increased from 5.3 +/- 0.3 to 6.2 +/- 0.7 (p <0.01). Mean calcium excretion decreased from 3.5 +/- 2.7 to 2.5 +/- 2.7 mg./kg. (p <0.05). At an average followup of 22 months (range 3 to 67) the recurrence rate in the group overall was 0.07 per patient-year. The previous recurrence rate of 0.32 per patient-year in the 20 children with a history of recurrent stone disease decreased to 0.17 per patient-year after treatment. None of the 44 initial stone formers had recurrent stones. CONCLUSIONS Our results show the safety and efficacy of oral potassium citrate treatment for restoring normal urinary citrate and suggest a preventive effect for recurrent calcium stone disease in children with hypocitruria and calcium stones.

The effect of nifedipine and verapamil on rhythmic contractions of human isolated ureter

The effect of calcium antagonists nifedipine and verapamil on spontaneous rhythmic contractions of human isolated ureter obtained from donor subjects undergoing kidney transplantation was investigated in comparison with a nonsteroidal antiinflammatory drug indomethacin. Stop-times i.e. the time elapsing from application, were determined for each drug. The rank order of potency at 10(-8) and 10(-7) M concentrations of the drugs was: nifedipine > verapamil > or = indomethacin. However, no significant difference of the stop-times was observed at 10(-6) M concentration of the drugs tested. The rhythmic contractions were re-activated by PGF2 alpha after stoppage with indomethacin but not with nifedipine or verapamil. These results suggest that not only endogenous PG synthesis but also an influx of calcium from the extracellular space is responsible for the spontaneous rhythmic activity of human ureter. The beneficial effects of using calcium antagonists in the treatment of ureteric colic is discussed.

Carotid intima–media thickness in children and young adults with renal transplant: Internal carotid artery vs. common carotid artery

Abstract:  Cardiovascular diseases are the main causes of morbidity and mortality following renal transplantation. Atherosclerotic structural changes, which can be detected by high‐resolution B‐mode ultrasonography, begin before clinical findings. However, little is known about the extent of these abnormalities in children after renal transplantation. We aimed to determine early structural changes of large arteries in renal transplant recipients without cardiovascular disease and to evaluate the role of clinical and laboratory features on IMT of carotid arteries. IMT and hemoglobin, serum levels of creatinine, acute phase proteins, lipid profile, and homocysteine were examined in 24 asymptomatic renal transplant recipients (median age 16.5 yr; range 8–25), and 20 healthy controls (median age 16 yr; range 9–24). CCA and ICA were evaluated in patients and controls with a high‐resolution B‐mode ultrasonography in multiple projections to optimize detection of carotid IMT. Measurement of IMT of both CCA [0.36 mm (range 0.16–0.48) vs. 0.28 mm (range 0.21–0.35), p < 0.001] and ICA [0.27 mm (range 0.16–0.48) vs. 0.22 mm (range 0.1–0.26), p < 0.001] were significantly higher in renal recipients than in healthy controls. Among several parameters assessed, only significant correlations were found between duration of CRF, duration of dialysis prior to transplantation and ICA‐IMT (p = 0.06 and p = 0.02, respectively) and between mean past serum calcium–phosphorus ion product and CCA‐IMT (p = 0.002). In conclusion, our observations indicate that vascular changes begin early in the course of CRF and are directly related to time on CRF and dialysis. These changes can be detected by measuring CCA/ICA‐IMT ultrasonographically. We suggest that early renal transplantation can potentially avoid long‐term cardiovascular events in children with end stage kidney disease.

The role of the pathologist in the evaluation of radical prostatectomy specimens.

Objective: To compare the difference between the routinely reported pathology records and the results of re‐evaluation of the same radical retropubic prostatectomy (RRP) specimens. Material and Methods: The RRP specimens of 114 patients initially reported by a general pathologist for routine purposes were re‐examined and re‐evaluated blindly with respect to the following parameters: organ confinement; capsular invasion; seminal vesicle invasion; lymph node metastasis; surgical margin positivity; Gleason grade and pathologic stage. Repeat and step sections were performed where necessary. Prostate mapping was done for each patient. Results: A statistically significant discordance between the routine evaluation and the re‐evaluation was observed with regard to capsular invasion, organ confinement, Gleason grade and pathologic stage. In addition to pathologic stage, Gleason grade and surgical margin positivity became significant prognostic factors after the re‐evaluation. Conclusions: RRP specimens should be evaluated by an expert prostate pathologist by submitting whole prostate specimens and should include detailed prostate mapping.

Preoperative Evaluation of Hilar Vessel Anatomy With 3-D Computerized Tomography in Living Kidney Donors

OBJECTIVES Digital subtract angiography is the gold standard for anatomic assessment of renal vasculature for living renal donors. However, multidetector-row computerized tomography (MDCT) is less invasive than digital subtract angiography and provides information of kidney stones and other intra-abdominal organs. In this study, preoperative MDCT angiography results were compared with the peroperative findings to evaluate the accuracy of MDCT for the evaluation of renal anatomy. METHODS From December 2002 to May 2007, all 60 consecutive living kidney donors were evaluated with MDCT angiography preoperatively. We reported the number and origin of renal arteries, presence of early branching arteries, and any intrinsic renal artery disease. Renal venous anatomy was evaluated for the presence of accessory, retroaortic, and circumaortic veins using venous phase axial images. The calyces and ureters were assessed with delayed topograms. The results of the MDCT angiography were compared with the peroperative findings. RESULTS A total of 67 renal arteries were seen peroperatively in 60 renal units. Preoperative MDCT angiography detected 64 of them. The two arteries not detected by MDCT had diameters less than 3 mm. Anatomic variations were present in nine veins, five of which were detected by CT angiography. Sensitivity of MDCT angiography for arteries and veins was 95% and 93%, respectively. Positive predictive values were 100% for both arteries and veins. CONCLUSION MDCT angiography offers a less invasive, rapid, and accurate preoperative investigation modality for vascular anatomy in living kidney donors. It also provides sufficient information about extrarenal anatomy important for donor surgery.

CYSTINE CALCULI IN CHILDREN: THE RESULTS OF A METABOLIC EVALUATION AND RESPONSE TO MEDICAL THERAPY

PURPOSE We describe baseline metabolic abnormalities and evaluate mercaptopropionylglycine plus potassium citrate treatment for urinary abnormalities and to prevent new stone formation in children with cystine stones. MATERIALS AND METHODS Daily urinary excretions of calcium, oxalate, citrate, magnesium, urate and phosphorus were determined in 18 children with cystine stone and 24 healthy children. The cystine stone cases were treated with 10 to 15 mg./kg. alpha-mercaptopropionylglycine and 1 mEq./kg. potassium citrate daily for a median 15 months. The potassium citrate dose was adjusted to render urinary pH 6.5 to 7.5. RESULTS There was no significant difference in baseline metabolic profile between the cystine stone and control groups except for citrate. The cystine stone group excreted less citrate than the control group (p = 0.044). After treatment median plus or minus standard deviation urinary cystine 245 +/- 233 to 140 +/- 106 mmol./mol. creatinine decreased from (p = 0.015), and urinary citrate increased from 255 +/- 219 to 729 +/- 494 mg./1.73 m.2 (p = 0.003). No serious adverse reaction was noted. Of the 15 patients with followup data 5 (33%) had 8 recurrent calculi (recurrence rate 0.64 per patient year). CONCLUSIONS Our results suggest that further investigation of low citrate excretion is needed in cystinuric children. Potassium citrate therapy is effective in increasing urinary pH and urinary citrate. However, high recurrence rate and persistent cystinuria in our patients emphasize the inadequacy of our treatment schedule in the prevention of recurrent cystine calculi.

Utility of the Doppler ultrasound parameter, resistive index, in renal transplant histopathology.

BACKGROUND Doppler ultrasonography is routinely used by many clinicians during long-term follow-up to identify high-risk patients without diagnosing the exact cause of graft dysfunction. Despite a number of studies showing a correlation between intrarenal resistive index (RI) and renal function in patients with kidney diseases, correlations between RI and renal histopathologic characteristics have not been sufficiently evaluated in renal transplant recipients. The aim of this study was to examine this relationship in grafted kidneys. PATIENTS AND METHODS The intrarenal RI was retrospectively compared with biopsy findings in 28 kidney recipients. All renal biopsy specimens were reviewed by light microscopy and immunofluorescence staining. For glomerulosclerosis, we considered the percentage of glomeruli showing this change; for interstitial fibrosis/tubular atrophy and interstitial infiltration, we graded abnormalities according to the methods of Kliem et al (Kidney Int 49:666, 1996). RESULTS The percentage of globally sclerosed glomeruli was significantly greater among patients with RI values higher than 0.75 than below this level (23% vs 47%; P = .022). Patients with grade 1 interstitial fibrosis and tubular atrophy (n = 14) showed lower RI values (0.68 +/- 0.03 vs 0.74 +/- 0.06; P = .047) than those with grade 3 fibrosis (n = 12). Similarly, lower RI values (0.66 +/- 0.02 vs 0.73 +/- 0.05; P = .014) were observed among patients with grade 1 (n = 13) compared with grade 3 interstitial infiltration (n = 13). CONCLUSION RI seemed to provide a prognostic marker for the graft rather than yielding an exact diagnosis of renal graft dysfunction.