Renal colic, where is it headed? An observational study.

AIM: In the last thirty years, the treatment for renal and ureteral calculi has undergone profound variations. The objective of this study has been to evaluate the existence of parameters which can affect the spontaneous expulsion of a symptomatic ureteral stone in a reasonably brief period of time and to identify whether certain parameters such as sex, age, the location and dimension of the stone, the presence of dilation in the urinary tract together with the administered therapy, can be used for a correct clinical management of the patient. METHODS: In a period of 9 months, 486 cases of renal colic were registered at emergency department. RESULTS: The cases of renal colic due to ureteral calculus were 188 (38.7%). The patients' charts, complete of all data and therefore, valid for this research, resulted to be 120 (64%). In the presence of a symptomatic ureteral stone, the correct approach must first of all, focalize on the dimension of the calculus itself; less importance instead, is given to the location, as reported in other studies, the presence of hydroureteronephrosis, sex and the side. CONCLUSION: In the cases when the pain symptoms cannot be solved by means of the administration of analgesics, it is then reasonable to take into consideration an immediate endourological treatment. If the pain symptoms are promptly solved, an attentive wait of 4 weeks should be considered reasonable in order to allow spontaneous expulsion of the calculus.

The endourological treatment of renal matrix stones.

OBJECTIVE: To report our experience with the endourological treatment of renal matrix stones, an infrequent form of urinary calculi whose diagnosis and treatment are often difficult. METHODS: From 1990 to 2010 we treated 9 female patients with matrix calculi using the endourological approach; 4 presented with renal colics, 3 with symptomatic urinary tract infection and 2 with asymptomatic bacteriuria. Six patients underwent percutaneous lithotripsy and 3 retrograde intrarenal surgery as first-line therapy. Three cases needed a multidisciplinary approach. RESULTS: The six percutaneous procedures were successful after a single session, while the retrograde approach required multiple treatments; a single case needed a shock wave session to complete the fragmentation, in another one a percutaneous lithotripsy was necessary after the first procedure, and a third case needed multidisciplinary treatment. CONCLUSIONS: Percutaneous lithotripsy has been confirmed as the first option for matrix stones. The retrograde approach - by confirming the suspected diagnosis and being minimally invasive - may be employed to treat either lower-size stones or stones at high risk of recurrence.

Renal biopsy in chronic kidney disease: lessons from a large Italian registry.

BACKGROUND: Renal biopsy procedure in patients with chronic renal failure (CRF) may represent a valid tool to help clinicians in clinical practice. However, the use of this invasive method in CRF is variable and it reflects the hospital biopsy policy. METHODS: To better define the CRF-related histological patterns and to assess the clinical utility of this procedure in this extensive group, we analyzed biopsy records of 1,185 CRF patients living in a large area of north-east Italy from 1998 to 2010. RESULTS: Data analysis showed that, although the biopsy incidence rate and the histological features were unchanged, the mean age of our CRF patients increased during the study period (R(2) = 0.42, p < 0.01). Primary and secondary glomerulonephritis (SGNs) were the main histological presentations (53.9 and 23%, respectively). SGNs were over-diagnosed in females. Leading histological types were immunoglobulin A nephropathy (22%), focal segmental glomerulosclerosis (12.4%), membranous glomerulonephritis (MGN, 7.5%) and nephroangiosclerosis (7.3%). These forms were also highly frequent in CRF patients with elevated proteinuria and moderate/severe renal damage. Elderly patients were primarily affected by MGN. After biopsy, 49.5% of CRF patients with and 34.1% without nephrotic syndrome received immunosuppression therapy. CONCLUSIONS: This study demonstrated that renal biopsy in CRF patients, regardless of age and glomerular filtration rates, is safe and essential to achieve a correct diagnosis and to commence the correct therapy. Additionally, it revealed that, even in patients with severe renal damage, it is possible to perform an accurate histological diagnosis and, interestingly, end-stage kidney disease seems not to be the primary form.

Incidence of primary glomerulonephritis in a large North-Eastern Italian area: a 13-year renal biopsy study.

BACKGROUND: The reported incidence of biopsy-proven primary glomerulonephritis (PGN) varies according to geographical, temporal and environmental factors. Consequently, the development of national/regional registers may help clinicians and researchers to improve knowledge about this important clinical condition. METHODS: To better define the epidemiology of PGN in our North-Eastern Italian area (∼5 million inhabitants), we evaluated the kidney biopsy records of 2680 adult patients with PGN diagnosis reported from 1998 to 2010 in the 'Triveneto' Register of Renal Biopsies. RESULTS: Statistical analysis showed that the mean age of patients undergoing renal biopsy was gradually increased from 1998 to 2010 (R(2) = 0.82, P < 0.01) with a growing percentage of those aged over 65 years (R(2) = 0.72, P < 0.01). According to the clinical presentation of our PGN patients, we found a significant increase in biopsies performed for acute renal failure (P < 0.01) and a decrement of those for macroscopic haematuria (P < 0.01) and nephritic syndrome (P = 0.04). Moreover, although there has been an unchanged total annual rate of biopsy-proven PGN (P = 0.47), there has been a significant enhancement in the incidence of minimal change disease (MCD, P = 0.04) and extracapillary proliferative glomerulonephritis (ExGN, P = 0.03) over time primarily due to a progressive increase in the mean age of patients affected by both renal diseases. Immunoglobulin A (IgA) nephropathy was the most common glomerulonephritis. CONCLUSIONS: Therefore, even if the number of PGN did not diminish during the 13-year study period, we reported considerable changes in the demographical and clinical characteristics of our biopsied patients (older and with acute kidney injury). Additionally, we found a change in the bioptic pattern of our patients over time with a progressive rise of some histological features such as MCD and ExGN. This may reflect not only the progressive ageing of our nephrology patients, but also a change in the biopsy policy of local hospitals.

Long-term treatment with potassium citrate and renal stones in medullary sponge kidney.

BACKGROUND AND OBJECTIVES: Medullary sponge kidney (MSK) is a renal malformation typically associated with nephrocalcinosis and recurrent calcium stones. Incomplete distal renal tubular acidosis, hypocitraturia, and hypercalciuria are common. For stone prevention, patients with MSK generally receive the standard "stone clinic" recommendations and often receive potassium citrate (KC). However, the effect on stone recurrence of citrate treatment in these patients has never been studied. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The issue was retrospectively analyzed on an outpatient basis in 97 patients with a radiologic diagnosis of MSK: 65 had at least one stone risk factor (SRF; hypercalciuria, hypocitraturia, hyperuricosuria, hyperoxaluria) and received KC [29 +/- 8 (SD) mEq/d]; 10 patients with SRF and 22 without received only general stone clinic suggestions. Follow-up was 78 +/- 13, 72 +/- 15, and 83 +/- 14 months, respectively. The 24-hour urinary excretion of calcium, oxalate, uric acid, citrate, and morning urine pH were investigated at baseline and at the end of follow-up. RESULTS: Parallel to a significant rise in urinary citrate and decreased urinary calcium (all P < 0.001), KC led to a dramatic reduction in the stone event rate (from 0.58 to 0.10 stones/yr per patient). The existence of a group of patients with MSK, those without SRF, with a very low stone rate and no SRF was recognized. CONCLUSIONS: Treatment with KC is effective in preventing renal stones in the typical patient with MSK. It seems that two clinical phenotypes among patients showing typical MSK features during radiologic study exist.

Primary IgA nephropathy is more severe in TGF-beta1 high secretor patients.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and is characterized by extremely variable clinical and morphological features and outcome. TGF-beta1 has a key role in fibrogenesis and the progression of renal damage. Its production is under genetic control. METHODS: We recruited 105 Italian biopsy-proven IgAN patients for genotyping for the TGF-beta1 C-509T, T869C (COD 10) and G915C (COD 25) polymorphisms; 200 healthy blood donors were used as normal controls. Glomerular and interstitial mRNA levels of TGF-beta1 were assessed by real-time PCR in 34 patients to seek relationships with clinical, renal histopathological features and outcome. RESULTS: The genotype distributions in the IgAN population were not statistically different from the controls. The COD 10 TT genotype was associated with more severe histological damage as assessed by Lee's classification (CC 50%, CT 39.6% and TT 17.2% were graded as mild; CC 35.7%, CT 43.7% and TT 44.8% as moderate, and CC 14.3%, CT 16.7% and TT 37.9% as severe [p=0.0049]) and with severe interstitial infiltrates (CC 10.4%, CT 35.2% and TT 54.2% [p=0.03]). A higher interstitial immunodeposition was observed for TGF-beta1, collagen IV and alpha-SMA in patients with the COD 10 T allele (p=0.045, p=0.049, p=0.032, respectively). The T allele was associated with significantly higher TGF-beta1 mRNA levels in the interstitium (TT+CT vs. CC: 0.52 +/- 0.16 vs. 0.18 +/- 0.10 copies/mL, respectively; p=0.000). The T allele was also associated with higher mRNA levels in glomeruli, though the difference was not statistically significant. Finally, the T allele was significantly associated with a worse prognosis, the end points being reached by 40% of TT+CT and 32% of CC patients (p=0.009). CONCLUSIONS: In primary IgA nephropathy, the T allele of the TGF-beta1 COD 10 C/T polymorphism seems to be associated with more severe histological lesions, higher renal TGF-beta1 mRNA levels and a worse prognosis. This polymorphism seems to be functionally relevant and to have a prognostic impact.

Bone disease in medullary sponge kidney and effect of potassium citrate treatment.

BACKGROUND AND OBJECTIVES: In medullary sponge kidney (MSK)-a common malformative renal condition in patients with calcium nephrolithiasis-hypercalciuria, incomplete distal renal tubular acidosis, and hypocitraturia are common. Clinical conditions with concomitant hypercalciuria and/or incomplete distal renal tubular acidosis are almost invariably associated with bone disease, making osteopathy highly likely in MSK, too. Patients with MSK have never been investigated for osteopathy; neither has the potential effect of potassium citrate administration (CA) on their urinary metabolic risk factors and on bone mineralization. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: These issues were retrospectively analyzed in 75 patients with MSK and primary stone risk factor (PSRF; hypercalciuria, hypocitraturia, hyperuricosuria, and/or hyperoxaluria) on an outpatient basis; 65 received CA (2.9 +/- 0.8 g/d), whereas 10 received only general "stone clinic" suggestions. The 24-h urinary excretion of calcium, phosphate, oxalate, uric acid, and citrate; morning urine pH; serum biochemistry; and bone mineral density were investigated at baseline and at the end of follow-up (78 +/- 13 and 72 +/- 15 mo in groups A and B, respectively). RESULTS: CA led to a significant rise in urinary pH and citrate and decreased urinary calcium and phosphate (all P < 0.001). Patients with MSK and PSRF had reduced bone density. Bone density improved significantly in the group that was treated with oral CA. CONCLUSIONS: Bone disease is very frequent in patients with MSK and concomitant PSRF. Long-term CA improves bone density. The concurrent effects of treatment on PSRF suggest that the subtle acidosis plays a pivotal role in bone disease and hypercalciuria in patients with MSK.

Unusual renal presentation of Fabry disease in a female patient.

BACKGROUND: A 29-year-old white woman with a family history of Fabry disease was referred to a nephrology clinic with hypertension and nephropathy. Her renal function was below normal (serum creatinine level 141 micromol/l; estimated glomerular filtration rate 41 ml/min/1.73 m2) with no proteinuria or albuminuria. INVESTIGATIONS: Medical history, physical examination, leukocyte alpha-galactosidase A assay, laboratory tests (for antinuclear antibodies, antineutrophil cytoplasmic antibodies, lupus anticoagulant, anticardiolipin antibodies, complement and cryoglobulin), ophthalmological examination, echocardiography, brain magnetic resonance angiography, renal ultrasonography, renal color echo-Doppler scan, renal magnetic resonance angiography, renal angiography and renal biopsy. DIAGNOSIS: Diffuse sclero-atrophic renal tissue changes and widespread renal arterio-arteriolosclerotic changes secondary to Fabry disease. TREATMENT: Angiotensin-converting-enzyme inhibitors and maintenance treatment with agalsidase-beta, 1 mg/kg body weight, every 2 weeks.

Precocious activation of genes of the renin-angiotensin system and the fibrogenic cascade in IgA glomerulonephritis.

BACKGROUND: The renin-angiotensin system (RAS) seems to play a pivotal role in progression of immunoglobulin A (IgA) nephropathy (IgAN). Accordingly, in patients with IgAN a relationship between the RAS and the fibrogenic cascade triggered by transforming growth factor-beta1 (TGF-beta1) should be observed. This study was carried out to obtain deeper insight into the regulation of RAS and the interaction with TGF-beta1 in the diseased kidney. METHODS: Twenty renal biopsies from IgAN patients and five from renal cancer patients (controls) were analyzed in both microdissected glomerular and tubulointerstitial compartments by reverse transcription-polymerase chain reaction (RT-PCR). All patients had normal renal function. The expression of the following genes was determined: angiotensinogen (Agtg), renin, angiotensin-converting enzyme (ACE), angiotensin II (Ang II) type 1 and type II (AT1 and AT2 receptors), TGF-beta1, collagen IV (Coll IV), alpha-smooth muscle actin (alpha-SMA). Quantitative data were confirmed for TGF-beta1 and ACE genes by real-time PCR. Results. RAS genes were overexpressed in IgAN patients vs. control subjects. There was no difference between glomerular and tubulointerstitial RAS gene expression levels. On the contrary, the overactivation of fibrogenic cascade genes (TGF-beta1, Coll IV, alpha-SMA) in the tubulointerstitium was observed (TGF-beta1, glomerular 0.14 +/- 0.10 SD; tubulointerstial 0.34 +/- 0.20; P = 0.000) (alpha-SMA, glomerular 0.08 +/- 0.07; tubulointerstitial 0.35 +/- 0.19; P = 0.000) (Coll IV, glomerular 0.12 +/- 0.11; tubulointerstitial 0.22 +/- 0.10; P = 0.03). This fibrogenic cascade seems to be triggered by RAS as indicated by statistically significant correlations between the expression of their respective genes. A direct relationship between the putative Ang II activity and the expression of AT receptor genes was found in the tubulointerstitium, whereas in the glomeruli this relationship was negative. In the interstitium, statistically significant positive relationships emerged between interstitial infiltrates and the gene expression of Agtg, AT1 receptor, Coll IV, and TGF-beta1. CONCLUSION: This study demonstrates that a tight regulation of the intrarenal RAS exists in IgAN and that it follows the general rules disclosed in animal models. Moreover, the RAS seems to be activated early in the diseased kidney and it appears that such activation drives inflammation and a parallel stimulation of the TGF-beta fibrogenic loop, particularly at the tubulointerstitial level.

Lessons from large interventional trials on antihypertensive therapy in chronic renal disease.

Studies in animal models have shown a convincing role for hypertension in the progression of renal disease. However, in clinical studies, the relationship between hypertension and progression is difficult to demonstrate owing to confounding factors such as age, gender, race, difficulty in identifying blood pressure (BP) parameters that correlate with progression, abnormal circadian BP pattern, and many non-haemodynamic factors of progression. A recent meta-analysis of several studies has shown that pharmacological agents that reduce both BP and proteinuria (U(P)), particularly angiotensin-converting-enzyme (ACE) inhibitors, significantly slow the rate of progression of chronic kidney disease. In these studies, lower achieved BP in patients both with and without U(P) was associated with slower decline in renal function. ACE inhibitors are effective BP-lowering agents and are associated with improved preservation of renal function compared with antihypertensive regimens without ACE inhibitors. The protective effect of ACE inhibition is additional to the effect of reducing BP and U(P).