Association of kidney and cysts dimensions with anthropometric and biochemical parameters in patients with ADPKD

Abstract

The aim of the study was to evaluate an association between kidney and cyst dimensions and anthropometric, clinical and biochemical parameters of autosomal dominant polycystic kidney disease (ADPKD) patients. Forty-nine adults, ADPKD-diagnosed patients aged 36 ± 11 years, and 50 healthy controls were included in the study. Oral glucose tolerance test (OGTT with 75 g of glucose) was performed and venous blood was collected to measure biochemical parameters and various ion concentrations. Ultrasound abdominal examinations were performed with special emphasis on kidney and cysts parameters. In the ADPKD group, mean kidney length correlated positively with age, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose and glucose and C-peptide concentrations after 120 min of glucose intake and negatively with Mg²⁺ concentration and glomerular filtration rate (eGFR). Multivariate analyses adjusted for age and gender showed that higher mean kidney length and maximal cyst diameter were significant predictors of higher SBP (p = 0.034 and 0.046, respectively) and DBP (p = 0.024 and 0.034, respectively), higher maximal cyst diameter was a significant predictor of higher OGTT 2-h C-peptide concentration (p = 0.033), higher mean cyst diameter was a significant predictor of lower eGFR (p = 0.039) and higher mean kidney length was a significant predictor of lower serum magnesium concentration (p = 0.043). In the ADPKD patients with normal GFR, mean kidney length and mean cyst diameter measured by ultrasonography are associated negatively with GFR and positively with blood pressure. Higher mean kidney length and cyst diameter might be indicators of disorders of glucose and magnesium metabolism which precede renal failure in patients with ADPKD.

• ADPKD
• C-peptide
• glucose
• hypertension
• insulin
• kidney and cyst dimensions

Introduction

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic disorders and the most frequent inherited kidney disease. In Caucasians, the prevalence of ADPKD is estimated at 1:200 to 1:1000.1

Multiorgan involvement is observed in the disease, with extrarenal localization of the cysts found commonly in the liver, pancreas as well as cerebral aneurysm, cardiac valvular anomalies, colonic diverticula,2 bronchiectasis3 and some metabolic abnormalities.4

The presence of kidney cysts is a characteristic feature in ADPKD patients, necessary to establish the diagnosis.5 Cysts may cause abdominal pain, hematuria and infections difficult to diagnose.6

The number and diameter of cysts increases with age.7 Before the age of 30, kidneys of patients with ADPKD have single cyst; after the age of 40, kidneys have many cysts of different sizes. This continuous growth and expansion of cysts leads to progressive renal enlargement and subsequent loss of renal function.8 Half of patients with ADPKD in the age of 60 develop end-stage renal disease (ESRD) requiring renal replacement therapy.9 In developed countries, patients with ADPKD constitute 4–10% of all patients undergoing dialysis. In 2007, the percentage of patients with ADPKD among subjects undergoing chronic dialysis therapy in Poland was 9.27%.10

Introduction of new radiological techniques: computed tomography (CT) and magnetic resonance imaging (MRI) allowed for more precise evaluation of such parameters of polycystic kidneys as: total kidney volume (TKV),11^,12 total cystic volume (TCV)13 and kidney parenchymal volume (KPV).14 In some studies, authors showed the relationship of these parameters with GFR in ADPKD patients, therefore, they might potentially serve as predictors of renal excretory function.15^,16

Because of high prevalence of hypertension in ADPKD patients (50–75%), which precedes renal failure,17 some studies analyzed the relationship between kidney structure, the activation of renin angiotensin aldosterone (RAA) system and hypertension.18 It was shown that in patients with ADPKD renal volume was significantly greater in the hypertensive patients compared to the group without hypertension.19

In spite of new diagnostic techniques (CT, MRI) assessing kidney volume, in clinical practice the evaluation of kidney length and cyst diameter is easily available using ultrasonography. The aim of the study was to search for associations of the number of cysts and their size with kidney length, anthropometric, clinical and biochemical parameters of patients with ADPKD before kidney failure.

Material and methods

Forty-nine adult, ADPKD-diagnosed patients (30 females and 19 males), aged 18–61 years, were enrolled, while the control group comprised 50 gender- and age-matched healthy individuals (28 females and 22 males) specifically recruited for this study. The inclusion criteria for the ADPKD group were as follows: the presence of cysts in both kidneys, allowing a diagnosis of PKD according to Ravine et al.,5 and a family history of ADPKD. Exclusion criteria were: serum creatinine ≥1.35 mg/dL, and a positive history of diabetes. As controls, individuals with a negative family history of ADPKD, the absence of kidney cysts fulfilling Ravine criteria (subjects with other cysts were not excluded), serum creatinine <1.35 mg/dL and no prior diagnosis of diabetes were recruited. Each participating individual was thoroughly informed about the study methods and objectives and personally granted his/her written consent to participate in the study. The study protocol was approved by the Ethical Committee of the Pomeranian Medical University, Szczecin, Poland (approval No. 001/135/06).

At the start of the study, morphometric parameters were recorded (body mass and height) and the body mass index (BMI) was calculated.

Blood pressure was measured three times on different days in the left arm using a standard mercury sphygmomanometer, in the sitting position, after a 10-min rest with a mean value used in analyses. Hypertension was defined as the use of a hypertensive medication or systolic/diastolic blood pressure ≥ 140/90 mmHg.

Oral glucose tolerance test (OGTT) was performed on another day, according to WHO guidelines (with 75 g of glucose).20 Before glucose administration (minute 0 of the test), venous blood was collected to measure glucose, insulin, C-peptide and creatinine concentration. After 120 min of glucose intake a second venous blood collection for glucose, insulin and C-peptide concentrations was performed. The analysis of glucose was performed by an enzymatic-amperometric method (Super GL device, Müller Gerätebau, Freital, Germany). Insulin was quantified by a microparticle enzyme immunoassay (MEIA, 2 D01-20, Axsym, Abbott, Warsaw, Poland) and C-peptide by electrochemiluminescent method (ECLIA, reagent kit and Cobas 6000 system from Roche, Warsaw, Poland). The serum concentrations of Na⁺, K⁺, Mg²⁺ ions and inorganic phosphate (Pi) were determined with an indirect ion-selective method using the Cobas Integra 800 bioanalyzer (Roche, reagents of Roche company). Ca²⁺ concentrations in serum were estimated with a direct ion-selective method using the CIBA-Corning 634 analyzer (Bayer, Warsaw, Poland). Serum creatinine concentrations were measured with the Cobas Integra 800 bioanalyzer (Roche).

Estimated glomerular filtration rate (eGFR) was calculated basing on a single serum creatinine measurement using the modification of diet in renal disease (MDRD) simplified formula.21

Ultrasound abdominal examinations (ultrasonographical apparatus SSA-660A/LC type, Toshiba, Zoetermeer, The Netherlands) were performed with special emphasis on kidney length, number and size of kidney and liver cysts. Maximal cyst diameter of both kidneys was noted in each patient (in controls without kidney cysts value “0” was used for statistical calculation). Mean cyst diameter was calculated for each kidney and mean of these two values was further analyzed (kidneys without cysts were not included in this analysis). Mean length of left and right kidneys was calculated. All sonographic measurements in ADPKD patients and controls were performed by the same experienced radiologist.

Statistics

As quantitative variables were not distributed normally, Mann–Whitney test was used to compare them between groups, while Fisher exact test was implemented for qualitative variables. Spearman rank correlation coefficient (Rs) was used to analyze correlations between quantitative variables. Multivariate analyses were performed with general linear model (GLM). Maximal and mean cyst diameters were transformed logarithmically before GLM analyses to normalize their distributions. Results with p <  0.05 were considered statistically significant. Data are presented as number (percentage) for qualitative variables or mean ± standard deviation for quantitative variables. Statistica 10 software (Stat Soft, Kraków, Poland) was used for all statistical analyses.

Results

Age, gender distribution, BMI, eGFR, insulin and C-peptide concentrations during 2-h OGTT were similar in ADPKD patients and controls. Fasting glucose and Ca²⁺ serum concentrations proved significantly higher, while Mg²⁺ serum concentration was significantly lower in ADPKD group than in controls. Moreover, in the ADPKD group arterial hypertension was notably more common than among controls, and both systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were significantly higher (Table 1).

Table 1. Clinical and biochemical characteristics of the ADPKD patients and the control group.

Parameters	ADPKD group (n = 49)	Control group (n = 50)	p-value^a
Age (years)	35.9 ± 11.1	36.7 ± 9.2	0.62
Sex (% males)	19 (39%)	22 (44%)	0.68
BMI (kg/m^2)	25.1 ± 4.9	24.4 ± 3.7	0.63
Creatinine (mg/dL)	0.84 ± 0.18	0.80 ± 0.15	0.54
eGFRMDRD  [mL/min/1.73 m^2]	98.0 ± 21.1	103.1 ± 19.9	0.27
Hypertension	29 (59%)	4 (8%)	<0.00001
SBP (mmHg)	133.88 ± 19.77	122.16 ± 14.91	0.002
DBP (mmHg)	92.92 ± 12.43	82.86 ± 9.30	0.00005
Fasting glucose (mg/dL)	91.61 ± 10.53	87.45 ± 9.19	0.04
OGTT 2-h glucose  (mg/dL)	89.59 ± 21.37	97.87 ± 24.33	0.5
Fasting insulin (µU/mL)	9.00 ± 4.77	8.38 ± 4.47	0.42
OGTT 2-h insulin(µU/mL)	40.62 ± 48.05	48.7 ± 47.93	0.10
Fasting C-peptide (µU/mL)	2.26 ± 0.69	2.05 ± 0.67	0.097
OGTT 2-h C-peptide  (µU/mL)	7.52 ± 2.98	7.59 ± 2.97	0.94
Mg^2+ (mmol/L)	0.81 ± 0.09	0.85 ± 0.05	0.021

Notes: BMI, body mass index; DBP, diastole blood pressure; eGFR_MDRD, glomerular filtration rate estimated according to Modification of Diet in Renal Disease formula; Mg²⁺, magnesium; OGTT, oral glucose tolerance test; SBP, systole blood pressure. Data are given as mean ± SD or number (percentage) of patients.

^aADPKD versus control group; Fisher exact test for qualitative variables and Mann–Whitney test for quantitative variables were used.

In the ADPKD group, females and males had similar kidney length but ADPKD females demonstrated significantly higher maximal cyst diameter in comparison to ADPKD males. In the control group, males demonstrated significantly higher kidney length in comparison to females. There were no differences between ADPKD males and females as regards liver cyst number or mean diameter and no liver cysts were found in controls (Table 2). Pancreas cysts were found only in one female ADPKD patient (2% of ADPKD group).

Table 2. Kidney and cysts parameters of ADPKD patients and controls stratified by gender.

	ADPKD group (n = 49)			Control group (n = 50)
Parameter	Females (n=30)	Males (n=19)	p-value females vs. males	Females (n = 28)	Males (n = 22)	p-value females vs. males
Number of subjects with kidney cysts	30 (100%)	19 (100%)	1.0	5 (18%)	4 (18%)	1.0
Total number of cysts in both kidneys	4.8 ± 1.3	4.7 ± 1.1	0.59	0.3 ± 0.6	0.2 ± 0.4	0.93
Maximal kidney cyst diameter^a (mm)	56.3 ± 29.6	38.2 ± 17.2	0.034	3.0 ± 8.2	2.1 ± 4.7	0.95
Mean kidney cyst diameter^b (mm)	21.9 ± 11	18.7 ± 7.2	0.38	11.6 ± 3.2	11.8 ± 2.1	0.61
Mean kidney length (mm)	147.8 ± 23.1	144.1 ± 20.5	0.59	109.2 ± 5.4	116.1 ± 5.9	0.00012
Number of subjects with liver cysts	15 (50%)	6 (32%)	0.25	0 (0%)	0 (0%)	1.0
Total number of cysts in liver	1.1 ± 1.3	0.6 ± 1.0	0.15	–	–	–
Mean liver cyst diameter^c (mm)	24.9 ± 15.1	17.5 ± 3.2	0.24	–	–	–

Notes: ^aIn controls without kidney cysts value “0” was used for calculation.

^bMean value was calculated for each kidney and mean of these values is presented. Kidneys without cysts were not included in the analysis.

^cLivers without cysts were not included in the analysis.

In the ADPKD group, mean kidney length correlated positively with age, SBP, DBP, fasting glucose and glucose and C-peptide concentrations after 120 min of glucose intake (2h-OGTT). Maximal cyst diameter correlated positively with age, SBP, DBP and 2h-OGTT C-peptide concentration (correlation with 2h-OGTT glucose was of borderline significance). Mean cyst diameter correlated positively with age, SBP, DBP and 2h-OGTT C-peptide concentration. Mean kidney length, maximal cyst diameter and mean cyst diameter correlated negatively with eGFR_MDRD. Mean kidney length and maximal cyst diameter correlated negatively with Mg²⁺ concentration, while mean cyst diameter correlated positively with K⁺ concentration (Table 3). Mean kidney length was strongly associated with maximal cyst diameter, mean cyst diameter and total number of cysts (Rs = 0.79, 0.75 and 0.75, respectively, with p < 0.00001 for each association).

Table 3. Correlations of kidney and cyst parameters with blood pressure values and biochemical parameters in ADPKD patients and controls.

	ADPKD group (n = 49)						Control group (n = 50)
	Mean kidney length		Maximal cyst diameter		Mean cyst diameter		Mean kidney length		Maximal cyst diameter		Mean cyst diameter
Parameters	Rs	p	Rs	p	Rs	p	Rs	p	Rs	p	Rs	p
Age	0.46	0.0082	0.33	0.02	0.44	0.0018	−0.03	0.85	−0.18	0.21	0.16	0.68
SBP	0.38	0.0064	0.34	0.017	0.39	0.0051	0.13	0.37	−0.16	0.27	0.25	0.52
DBP	0.37	0.008	0.26	0.069	0.37	0.0096	0.18	0.22	−0.05	0.75	0.07	0.85
Weight	0.21	0.15	0.09	0.55	0.25	0.087	0.61	<0.0001	−0.02	0.89	−0.13	0.74
Height	0.02	0.90	−0.17	0.24	0.01	0.97	0.57	<0.0001	0.03	0.86	−0.27	0.48
eGFRMDRD	−0.44	0.006	−0.38	0.0065	−0.49	0.00032	0.24	0.096	0.06	0.66	0.50	0.17
Fasting glucose	0.29	0.045	0.22	0.12	0.19	0.18	0.21	0.15	0.14	0.32	0.71	0.034
OGTT 2-h glucose	0.38	0.007	0.28	0.052	0.23	0.10	0.03	0.84	−0.08	0.58	0.37	0.33
Fasting insulin	0.08	0.59	0.14	0.32	−0.02	0.92	−0.03	0.83	0.07	0.62	0.07	0.87
OGTT 2-h insulin	0.13	0.37	0.20	0.18	0.06	0.67	−0.17	0.23	−0.041	0.77	0.44	0.24
Fasting C-peptide	0.26	0.066	0.22	0.13	0.16	0.27	0.12	0.42	−0.01	0.95	−0.12	0.76
OGTT 2-h C-peptide	0.33	0.021	0.44	0.0016	0.30	0.04	−0.25	0.083	−0.05	0.73	0.25	0.51
Na^+	0.22	0.14	0.13	0.39	0.15	0.32	0.29	0.039	0.00	0.98	0.58	0.10
K^+	0.18	0.23	0.24	0.091	0.39	0.0054	0.06	0.69	0.03	0.83	0.31	0.41
Ca^2+	0.14	0.35	0.06	0.69	0.15	0.29	0.15	0.31	0.16	0.27	−0.05	0.89
Mg^2+	−0.37	0.0095	−0.36	0.012	−0.23	0.11	0.26	0.069	0.09	0.53	0.26	0.50
Pi	−0.05	0.74	−0.03	0.87	−0.12	0.40	−0.36	0.0099	−0.09	0.54	−0.13	0.75

Notes: DBP, diastolic blood pressure; MDRD, modification of diet in renal disease formula; OGTT, oral glucose tolerance test; SBP, systolic blood pressure. Spearman's rank correlations coefficients (Rs) and corresponding p values are presented.

In controls, mean kidney length correlated with weight, height, Na⁺ (positively) and Pi (negatively), while mean cyst diameter correlated positively with fasting serum glucose (Table 3).

Multivariate analysis (GLM) with age and gender as independent variables showed that older age was a significant predictor of higher mean kidney length (p = 0.0010) and mean cyst diameter (p = 0.0019), while similar association with maximal cyst diameter did not reach statistical significance (p = 0.051). Association with gender was non-significant.

A series of GLM analyses adjusted for age and gender was performed to check whether associations of mean kidney length, mean or maximal cyst diameter (treated as independent variables) with other clinical parameters shown in Table 3 (treated as dependent variables) were independent of ADPKD patients' age and gender.

Higher mean cyst diameter (but not maximal cyst diameter or mean kidney length) was a significant predictor of lower eGFR_MDRD value, though older age was more significant predictor in this model (Table 4).

Table 4. GLM analysis of associations between gender, age and mean cyst diameter, treated as independent variables and glomerular filtration rate (GFR_MDRD) treated as dependent variable.

Independent variables	Beta	p
Female gender	−0.06	0.63
Age	−0.40	0.0042
Ln (mean cyst diameter)^a	−0.29	0.039

^aLogarithmical transformation was performed to normalize the distribution.

Higher mean kidney length and maximal cyst diameter were significant predictors of higher SBP (p = 0.034 and 0.046, respectively), but the association did not reach significance for mean cyst diameter (p = 0.056). However, similar association with diastolic blood pressure was significant for all three dimensions (p = 0.024, 0.034 and 0.019, respectively, Table 5). It should be noted that no association with SBP or DBP remained significant when the models were additionally adjusted for eGFR_MDRD.

Table 5. GLM analysis of associations between gender, age and mean cyst diameter, treated as independent variables and diastolic blood pressure (DBP) treated as dependent variable.

Independent variables	Beta	p
Female gender	−0.17	0.24
Age	+0.01	0.93
Ln (mean cyst diameter)^a	+0.37	0.019

^aLogarithmical transformation was performed to normalize the distribution.

Association of higher fasting and 2h-OGTT glucose with higher mean kidney length did not reach significance in GLM (p = 0.064 and p = 0.087, respectively). However, higher maximal cyst diameter was a significant predictor of higher OGTT 2h C-peptide concentration (p = 0.033).

Higher mean kidney length was a significant predictor of lower serum magnesium concentration (p = 0.043) and higher mean cyst diameter was a significant predictor of higher serum potassium concentration (p = 0.0090). Both associations remained significant (p = 0.043 and 0.0079, respectively) when the models were additionally adjusted for eGFR_MDRD and the use of diuretics.

In the ADPKD group, 21 patients with liver cysts were older (40.3 ± 8.1 vs. 32.5 ± 11.9 years, p = 0.013) had lower eGFR_MDRD (90.7 ± 18.7 vs. 103.4 ± 21.5 mL/min/1.73 m², p = 0.022) and higher 2h-OGTT glucose (97.2 ± 21.7 vs. 83.9 ± 19.6 mg/dL, p = 0.014) than 28 patients without liver cysts. However, in multivariate analysis adjusted for age and gender, the presence of liver cysts was no longer significantly associated with lower eGFR_MDRD (p = 0.39) or higher 2h-OGTT glucose (p = 0.09). In the subgroup of ADPKD patients with liver cysts their mean diameter correlated negatively with fasting glucose (Rs = −0.51, p = 0.019), insulin (Rs = −0.47, p = 0.032) and C-peptide (Rs = −0.48, p = 0.029) but no correlation with 2h-OGTT parameters was found. These three associations also lost significance in multivariate analysis adjusted for age and gender (p = 0.063, p = 0.11 and p = 0.052, respectively).

Discussion

Kidney length is proportional to body mass. In healthy subjects mean kidney length was 9.0–12.8 cm in females and 9.2–13.3 cm in males when measured by ultrasound22 and 11.6 ± 1.1 cm and 12.4 ± 0.9 cm, respectively, when using MRI.23 The absolute renal length was significantly greater in men than in women for both kidneys (p < 0.01), but when height and age were included in the multivariate regression analysis, sex was not a significant predictor of kidney length.24 In our control group, kidney length in males was higher than in females. Strong positive correlations between kidney length and body weight or height were observed in controls, but not in ADPKD patients. The lack of differences in kidney length between females and males in ADPKD group could have resulted at least partially from the presence of significantly bigger cysts in females (Table 2). It can also be hypothesized that kidney enlargement in an early stage of ADPKD appears earlier in females than in males. It is of note that our previous study concerning myocardial hypertrophy in the same group of ADPKD patients showed that left ventricular mass index was significantly increased only in females but not in males.25

We showed that kidney length and cyst diameter correlated positively with age in patients with ADPKD. Bivariate analysis with age and gender as independent variables showed that older age was a significant predictor of higher mean kidney length and mean cyst diameter. Results of our study are consistent with the results of the study of the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP), in which kidney structure was examined using MRI. Chapman et al. reported that the presence of ADPKD is characterized by significant cystic involvement that increases with age. In the CRISP cohort, total renal, cyst and non-cystic volume was significantly greater in the 25–34 year age group and in the 35–45 year age group as compared to the 15–24 year age group. As well, cyst and TKV were significantly greater in the 35–45 year group as compared to the 25–34 year age group.8

Studies of King et al.14 using fast electron-beam CT scanning showed that TKV and TCV correlated positively with age, while KPV and GFR correlated negatively with age. During the 8-year of follow-up, TKV and TCV increased, while KPV and GFR declined. There was a significant correlation between the rate of increase in renal cyst volume and the rate of decline in GFR. Our results also showed that kidney and cyst dimensions correlated negatively with GFR in ADPKD patients and the association with mean cyst diameter was independent of patients' age and gender. Nicolau et al.26 who examined patients with ADPKD (n = 213) and non-ADPKD subjects (n = 187) showed that the mean kidney length measured by ultrasound methods in individuals with normal serum creatinine was significantly smaller than the length of those with renal failure in the same age groups (16.5 ± 3.5 cm vs. 21.5 ± 4.8 cm, respectively, in patients under 40 years of age; 21.2 ± 5.1 vs. 25 ± 5.9 cm in patients 40 years of age and older).

Our results showed that in ADPKD patients, higher kidney length and cyst diameter were significant predictors of higher SBP and DBP, independent of age and gender. However, the significance of the associations with blood pressure was lost after additional adjustment for GFR.

Hypertension in ADPKD patients contributes to increase in kidney volume, proteinuria, number of cardiovascular events and impairment of kidney function leading to ESRD.11 Further studies are needed to evaluate the influence of progressive GFR decline (but still within normal limits), stimulation of RAA system and other potential mechanisms related probably to functional defects in polycystin-1 and -2, important for intracellular calcium homeostasis, on the development of systemic hypertension in patients with ADPKD.

It is well known that kidneys play an important role in glucose homeostasis.27 Patients with chronic kidney disease and without diabetes show impaired glucose tolerance. In these patients fasting glucose and insulin concentrations are normal or slightly increased, while proinsulin and C-peptide concentrations are significantly increased.28 In physiology, serum insulin and C-peptide molar concentrations are equal.29 Insulin is metabolized mainly in liver and C-peptide is degraded in kidneys. Insulin half-life is approximately 5 min, while the time is approximately 5–7-fold longer for C-peptide.30 In our patients with ADPKD and normal GFR, we showed positive correlations of mean kidney length and higher maximal cyst diameter with fasting concentrations of glucose and C-peptide (borderline significance) and with 2h-OGTT glucose and C-peptide concentrations (independent of age and gender). In literature, we found no data on the relationship between kidney length or cyst diameter and parameters of glucose metabolism in patients with ADPKD and normal GFR.

We have also found some associations between parameters of glucose metabolism and presence and size of liver cysts in ADPKD patients, but they lost significance in multivariate analysis. Negative correlations of mean liver cyst diameter with fasting glucose, insulin and C-peptide might be hypothetically explained by impaired gluconeogenesis in livers with big cysts, but further studies are needed to show whether and how liver cysts affect glucose metabolism in ADPKD patients.

It seems that in patients with ADPKD and normal GFR association of kidney enlargement with higher C-peptide concentration, both fasting (though on the border of significance) and after glucose load, could have been the result of its impaired renal metabolism due to changed kidney structure. On the other hand, positive correlations of kidney length and cyst diameter with higher fasting glucose and 2h-OGTT glucose could have been the result of impaired beta-cell function after an oral glucose load in ADPKD patients, observed in our previous study.31 We hypothesized that in patients with ADPKD the presence of mutated polycystin-1 and 2, serving as the ion channel for calcium, induced a decrease in calcium concentration inside cells and contributed to the impairment of insulin release from secretory granules. Recent studies both in vitro on human cells and in animal model showed intracellular disorders of glucose metabolism in patients with ADPKD.32

Moreover, in ADPKD group mean kidney length and maximal cyst diameter negatively correlated with serum magnesium concentration. Some authors33^,34 showed that proximal and distal tubular function parameters (Tm_Glucose, Tm_PAH, urinary acidification) were impaired in patients with ADPKD when GFR was normal, indicating tubular disruption by the cysts. We hypothesize that such defect of proximal tubule could also affect reabsorption of Mg²⁺. It could explain association of lower Mg²⁺ (due to its excessive renal loss) with larger cysts (due to more severe tubule damage), but is not consistent with positive correlation of mean cyst diameter and serum K⁺. It seems that associations between kidney or cyst diameters and magnesium metabolism are independent of associations with glucose metabolism since there was no correlation between serum magnesium concentration and glucose metabolism parameters in our ADPKD patients and controls (data not shown).

Studies using MRI and CT supply new information on the structure and excretory function of kidneys.14^,15^,25 However, in routine clinical practice ultrasonography is used because of lower costs and availability.35^,36 Our study with the use of ultrasound methods showed that mean kidney length and mean cyst diameter in patients with ADPKD might be good predictors of both excretory and metabolic kidney function. Its main limitation is small number of subjects. Further prospective studies with larger cohorts are needed to assess predictive value of kidney and cyst dimensions in ADPKD patients.

In conclusion, strong positive correlations between the number of cysts, their diameters and kidney length in patients with ADPKD and normal GFR show that increased kidney length reflects the degree of polycystic degeneration. In ADPKD patients with normal GFR, mean kidney length and mean cyst diameter measured by ultrasonography are associated negatively with GFR and positively with blood pressure. Further prospective studies are needed to establish predictive value of these parameters for the development of renal failure and hypertension.

Higher mean kidney length and cyst diameter might be indicators of disorders of glucose and magnesium metabolism which precede renal failure in patients with ADPKD.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.