Hans-Göran Tiselius

Medical Therapy to Facilitate the Passage of Stones: What Is the Evidence?

CONTEXT Medical expulsive therapy (MET) for urolithiasis has gained increasing attention in the last years. It has been suggested that the administration of alpha-adrenoreceptor antagonists (alpha-blockers) or calcium channel blockers augments stone expulsion rates and reduces colic events. OBJECTIVE To evaluate the efficacy and safety of MET with alpha-blockers and calcium channel blockers for upper urinary tract stones with and without prior extracorporeal shock wave lithotripsy (ESWL). EVIDENCE ACQUISITION A systematic review of the literature was performed in Medline, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews searched through 31 December 2008 without time limit. Efficacy and safety end points were evaluated in 47 randomised, controlled trials assessing the role of MET. Meta-analysis was conducted using Review Manager (RevMan) v.5.0 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). EVIDENCE SYNTHESIS Pooling of alpha-blocker and calcium channel blocker studies demonstrated a higher and faster expulsion rate compared to a control group (risk ratio [RR]: 1.45 vs 1.49; 95% confidence interval [CI]: 1.34-1.57 vs 1.33-1.66). Similar results have been obtained after ESWL (RR: 1.29 vs 1.57; 95% CI: 1.16-1.43 vs 1.21-2.04). Additionally, lower analgesic requirements, fewer colic episodes, and fewer hospitalisations were observed within treatment groups. CONCLUSIONS Pooled analyses suggest that MET with alpha-blockers or calcium channel blockers augments stone expulsion rates, reduces the time to stone expulsion, and lowers analgesia requirements for ureteral stones with and without ESWL for stones < or = 10 mm. There is some evidence that a combination of alpha-blockers and corticosteroids might be more effective than treatment with alpha-blockers alone. Renal stones after ESWL also seem to profit from MET. The vast majority of randomised studies incorporated into the present systematic review are small, single-centre studies, limiting the strength of our conclusions. Therefore, multicentre, randomised, placebo-controlled trials are needed.

Composition and clinically determined hardness of urinary tract stones

Objectives.To derive hardness factors for crystal phases of urinary tract stones and describe the hardness pattern in a stone population. Material and methods. In a retrospective study, recordings from patients treated with extracorporeal shock-wave lithotripsy (ESWL) (stone surface area ≤ 100 mm2) were used to derive hardness factors. The number of re-treatments, the number of shock waves and the energy index (the voltage in kilovolts multiplied by the number of shock waves) required for a satisfactory stone disintegration were assumed to reflect the hardness. The stone composition in 2100 patients provided the basis for an average hardness pattern. A hardness index was calculated from the fraction of each crystal phase and its hardness factor. Results. The hardness factors were as follows: calcium oxalate monohydrate, 1.3; calcium oxalate dehydrate, 1.0; hydroxyapatite, 1.1; brushite, 2.2; uric acid/urate, 1.0; cystine, 2.4; carbonate apatite, 1.3; magnesium ammonium phosphate, 1.0; and mixed infection stones, 1.0. The hardness index for 114 stones (surface area 100–200 mm2) corresponded reasonably well to the ESWL treatment efforts. Calcium oxalate monohydrate, calcium oxalate dihydrate and hydroxyapatite were the most frequently encountered crystal phases in all 2100 stones. Only 21% of the stones were composed of only one crystal phase. There were two, three and more than three crystal phases in 26%, 38% and 15% of the stones, respectively. The hardness index calculated for 2100 stones ranged between 0.70 and 2.33, with a mean (SD) of 1.18 (0.15). Conclusions. The hardness factors and hardness index derived in this study might be useful for describing the stone situation in individual patients and groups of patients and for comparison of various treatment strategies.

Patients’ attitudes on how to deal with the risk of future stone recurrences

One hundred consecutive patients referred for active stone removal responded to a number of questions regarding their attitude to metabolic risk evaluation and recurrence prevention. Of the 74 men and 26 women all but one were interested in the cause of their disease. While 95% of the patients were motivated to change their dietary habits, only 71% were interested in pharmacological treatment. Collection of 24-h urine for risk evaluation in one or five fractions was acceptable to 94 and 84% of the patients, respectively. Only 79% wanted to collect urine during more than one 24-h period. Given the option of a recurrence prevention programme or active stone removal when or if a stone appeared, approximately half of our patients (52%) chose the first, and about one-third (29%) of them chose the second alternative, whereas as many as 19% of the patients did not express any opinion. A programme for regular follow-up in order to detect new stones early was appreciated by only 81 patients. These results show that biochemical risk evaluation and recurrence prevention is generally met with a positive attitude by most patients and that medical recurrence prevention appears to be appreciated by more than half of the patients.

Simulating calcium salt precipitation in the nephron using chemical speciation

Theoretical modeling of urinary crystallization processes affords opportunities to create and investigate scenarios which would be extremely difficult or impossible to achieve in in vivo experiments. Researchers have previously hypothesized that calcium renal stone formation commences in the nephron. In the present study, concentrations of urinary components and pH ranges in different regions of the nephron were estimated from concentrations in blood combined with a knowledge of the renal handling of individual ions. These were used in the chemical speciation program JESS to determine the nature of the solution complexes in the different regions of the nephron and the saturation index (SI) of the stone-forming salts calcium oxalate (CaOx), brushite (Bru), hydroxyapatite (HAP) and octacalcium phosphate (OCP). The effect of independent precipitation of each of the latter on the SI values of other salts was also investigated. HAP was the only salt which was supersaturated throughout the nephron. All of the other salts were supersaturated only in the middle and distal regions of the collecting duct. Supersaturations were pH sensitive. When precipitation of CaOx, Bru and OCP was simulated in the distal part of the collecting duct, little or no effect on the SI values of the other stone forming salts was observed. However, simulation of HAP precipitation caused all other salts to become unsaturated. This suggests that if HAP precipitates, a pure stone comprising this component will ensue while if any of the other salts precipitates, a mixed CaOx/CaP stone will be formed. Application of Ostwald’s Rule of Stages predicts that the mixed stone is likely to be CaOx and Bru. Our modelling demonstrates that precipitation of stone-forming salts in the nephron is highly dependent on the delicate nature of the chemical equilibria which prevail and which are themselves highly dependent on pH and component concentrations.

A simple device (Hemostick®) for the standardized description of macroscopic haematuria Our initial experience

Objective. To evaluate the clinical use of a simple device (Hemostick) developed to enable a standardized description of the degree of macroscopic haematuria. Material and methods. The visual scale (Hemostick) used in this study comprised six colour fields, one yellow (blank; 0) and five with different nuances of red (1–5) selected from a colour scale according to clinical observations of samples obtained from patients with macroscopic haematuria. Urine samples containing blood were examined and given a Hemostick score (HS) of 0–5, based on comparison with the colour fields on the scale. In three experimental series, (A) 63, (B + C) 14 and (D) 60×4 urine samples were examined by observers. The reported HS was compared with the personal descriptions of the degree of haematuria. We also assessed the absorbance at 412 nm, the haemoglobin concentration and the number of erythrocytes. Results. In the first two series (A and B + C) comprising 325 observations on 77 urine samples, the HS for the same sample as reported by the observers was in agreement in 75–93% of cases. In Series B + C the coefficient of variation was 0.06 and the mode 2.68, which was almost identical to the observed mean HS value of 2.69. Based on observations on 240 urine samples considered by four observers during four consecutive days (Series D), an acceptable agreement was recorded in 74–94% of cases. In this experiment the mean HS differed from the mode by not more than 0.12–0.19. In terms of absorbance there was very good discrimination between samples with HSs 1, 2, 3 and 4. Measurements of the haemoglobin concentration (g/l) gave us the following approximate ranges for HSs 0, 1, 2, 3 and 4: <0.2, 0.2–1, 1–5, 5–25 and >25, respectively. Samples with HS 5 comprised those with a high concentration of old blood. Conclusions. The results of this series of experiments involving scoring of macroscopic haematuria were encouraging. The Hemostick device was easy to use and resulted in a satisfactory consensus regarding the degree of haematuria and one that was superior to that deduced from a personal terminology.

Chemolytic Treatment of Patients with Urinary Tract Stones

The combined use of extracorporeal shock wave lithotripsy (SWL) and percutaneous irrigation with chemolytic agents has proven useful for providing an extremely low-invasive therapeutic approach. This form of treatment can be applied in patients with large infection stones, as well as in patients with stones composed of brushite, cystine, and uric acid. Although other treatment options might be less time consuming, the chemolytic method is a definite alternative in selected patients for whom other procedures are either excluded or associated with a greater risk. Chemolytic irrigation also can be of great importance to clear the renal collecting system from stone fragments after percutaneous stone removal. For stones composed of uric acid, an entirely oral treatment can be used to accomplish stone removal in a completely noninvasive way. The principles and possibilities of chemolytic treatment are outlined in this chapter.

Editorial Comment on: Diet, Fluid, or Supplements for Secondary Prevention of Nephrolithiasis: A Systematic Review and Meta-Analysis of Randomized Trials

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