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Institut Institu t fr Balneologie und r nnove Medizinische Klimatologiechschule Ha Me diz he inisc Ho Effect of a bicabonate-rich mineral water in patients with recurrent renal stone formation a controlled double-blind study Chr. Gutenbrunner, U. Smorag, O. Karaglle, F. Candir, H. Becker, U. Jonas Professor Christoph Gutenbrunner, MD, PhD, Clinic for Physical Medicine and Rehabilitation Hanover Medical School Carl-Neuberg-Str. 1 D-30625 Hannover [email protected] Introduction Institut Institu t fr Balneologie und Medizinische Klimatologiechschule Me diz he inisc over Hann Ho In the industrialised countries urolithiasis is a frequent disease Prevalence in Germany: 4.7% Incidence: 1.47%

The rate of relapses is high: 50-60% The extra-corporal shock-wave therapy is not free of complications For that reason an effective metaphylaxis is of major importance Introduction Institut Institu t fr Balneologie und Medizinische Klimatologiechschule Me diz he inisc over Hann Ho A basic principle of the metaphylaxis of urolitioasis is the dilution of the urine by an increase of the fluid intake Additional principles are the reduction of the excretion of stone forming substances in the urine: calcium, oxalate, uric acid and others the enhancement of the excretion of inhibitors: magnesium, citrate and others the reduction of the crystallisation risk by influencing the pH of the urine (dependent on the type of renal stones) Introduction Institut Institu t fr Balneologie und Medizinische Klimatologiechschule Me diz he

inisc over Hann Ho From experimental studies it is known that bicarbonate waters increase the urinary pH and the citrate excretion magnesium-rich waters increase the urinary excretion of magnesium the increase of calcium-excretion is over- compensated by the increase of diuresis Only a few studies were performed in patients Most studies dealt with the problem of calcium-waters Therefore we studied the effect of a magnesium- and bicarbonate-rich mineral water Material and Methods Institut Institu t fr Balneologie und Medizinische Klimatologiechschule Me diz he inisc over Hann Ho Design of the Study: - double-blind controlled study - cross-over-design Patients: - Patients with multi-episodic CaOx-urolithiasis - males/females: 30/4 - number of stone episodes: 3.0 1.6 Setting: - Everyday activities

- no standardisation of the diet - nutrition protocol (n=34) Material and Methods Institut Institu t fr Balneologie und Medizinische Klimatologiechschule Me diz he inisc over Hann Ho Interventions: - 1.5 l/d bicarbonated water (2,673 mg HCO3-/l; mg Ca++/l) 175 mg Mg++/l; 116 - 1.5 l/d low-mineralized water (98 mg HCO3-/l Ca++/l) 8 mg Mg++/l; 38 mg - 1.400 ml of each water for three consecutive days - all waters in the same type of bottles, colour code - distance between drinking periods: one week Main Outcome Parameters: - 24-h-urine samples before drinking, 3 rd day of drinking - urinary pH (24-h-urine) - magnesium- and citrate-excretion - supersaturation CaOx and of other types of urinary stones Results Institut Institu t fr

Balneologie und Medizinische Klimatologiechschule Me diz he inisc over Hann Ho Patients with Recurrent Urolithiasis (n = 34) 8 7 Calcium-Excretion *** 70 60 6 50 5 40 4 7 6 Magnesium-Excretion *** 30 1100 1000 900 800 5 4 700 600 500 3 Oxalate-Excretion 400

* Citrate-Excretion *** Results Institut Institu t fr Balneologie und Medizinische Klimatologiechschule Me diz he inisc over Hann Ho Baseline Controls Baseline Bicarbonate Water Patients with Recurrent Urolithiasis n = 34 [l] Urinary Volume 4,0 Urinary pH 7,0 3,5 3,0 4,5 4,0 *** *** *** 3,5

6,5 3,0 2,5 * 6,0 2,5 2,0 2,0 1,5 5,5 1,0 Supersaturation CaOx 1,5 1,0 *** *** Results Institut Institu t fr Balneologie und Medizinische Klimatologiechschule Me diz he inisc over Hann Ho Supersaturation CaOx Supersaturation Uric acid Supersaturation CaPO4

Baseline 3,41 0,31 1,22 0,13 1,33 0,19 Drinking 2,44 0,28 0,70 0,07 1,01 0,15 Baseline 3,39 0,34 1,03 0,12 1,44 0,23 Drinking 2,42 0,29 0,24 0,04 2,01 0,24 0,801 0,001 0,001 Controls 0,001 0,001 0,014 Bicarbonate Water 0,001 0,001 0,023 Controls Bicarbonate Water p (controls vs. bicarbonate water)*)

p (baseline vs. Drinking)**) Patients with high risk Institut Institu t fr Balneologie und Medizinische Klimatologiechschule Me diz he inisc over Hann Ho Low mineralised water bicarbonate rich water Baseline Intervention Baseline Intervention Citrateconcentration (mmol/l) 1,73 0,88 1,18 0,43 1,61 0,72 1,60 0,56 Magnesiumconcentration (mmol/l) 2,18 0,92 Calciumconcentration (mmol/l) 3,15 1,68 Oxalateconcentration (mmol/l) 0,29 0,09

Uric acidconcentration (mmol/l) 1,77 0,67 Phosphateconcentration (mmol/l) 15,79 6,48 Significance p1 = 0,016** p2 = 0,001*** 1,53 0,49 p2 = 0,884 2,09 0,88 1,99 065 p1 = 0,033* p2 = 0,001*** 2,17 1,08 p2 = 0,961 3,07 1,37 2,57 1,27 p1 = 0,245 p2=0,001*** 0,21 0,10 p2=0,007** 0,28 0,12 0,21 0,09 p1 = 0,879 p2 = 0,002** 1,21 0,32 p2 = 0,001*** 1,49 0,37 1,36 0,40 p1 = 0,152 p2 = 0,001*** 10,86 3,29

p2 = 0,140 16,12 3,29 9,80 3,42 p1 = 0,231 p2 = 0,001*** p1 = Significance between verum and controls p2 = Significance between baseline and drinking period p2 = 0,001*** Conclusion Institut Institu t fr Balneologie und Medizinische Klimatologiechschule Me diz he inisc over Hann Ho Both waters significantly reduce the renal stone formation risk in patients with relapsing CaOx-urolithiasis The mineral water additionally increases the urinary pH as well as the excretion of magnesium and citrate The mineral water is effective even in cases with high risk of stone formation (hypercalciuria, hyperoxaluria) Bicarbonated waters should be used in patients with combined stones containing CaOx and uric acid or in uric acid stones but not in in patients with phosphate stones

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