Estimated glomerular filtration rates cannot replace measured GFR in type 1 diabetes patients with hyperfiltration.

AIM: This study of children and young adults with type 1 diabetes with normal to high glomerular filtration rates (GFR) compared estimated GFR (eGFR) with measured GFR (mGFR). METHODS: GFR was measured by inulin clearance, and we carried out simultaneous analyses of standardised creatinine and cystatin C. eGFR was calculated using different formulas. RESULTS: We enrolled 106 patients, including 56 males, aged 21.9 (standard deviation 9.2) years with 13.7 (9.1) years' duration of diabetes and a mean haemoglobin A1c (HbA1c ) of 7.7% (61 mmol/mol). The median mGFR was 128 (111-143) mL/min/1.73 m(2) . Most of the eGFR estimations failed to detect a significant proportion of hyperfiltration based on inulin clearance. The best accuracy (P30) between eGFR and mGFR was seen with eGFRCKD - EPI (92%), eGFRcys C Berg (86%), eGFRcys C CAPA (78%) and eGFRcys C Inker (84%) where eGFRCKD - EPI and eGFR cys C Berg showed the lowest bias. Most eGFRcys C measurements showed greater accuracy when combined with eGFRcr (P30 92-94%). CONCLUSION: The best accuracy (P30) and lowest bias were found with eGFRCKD - EPI and eGFR Berg. in this cohort. However, eGFR cannot accurately replace mGFR to detect hyperfiltration and follow GFR over time in young patients with type 1 diabetes.

Acute renal failure in dense deposit disease: complete recovery after combination therapy with immunosuppressant and plasma exchange.

We describe the clinical course of a female adolescent who was followed because of isolated microhematuria and hypocomplementemia before admission to hospital with a sudden onset of acute renal failure. At presentation, she exhibited complement consumption through the complement alternative pathway (AP) while other serologic tests were negative. Renal biopsy revealed dense deposit disease (DDD) with a crescentic pattern. Intravenous methylprednisolone, followed by plasma exchange (PE), and intravenous cyclophosphamide pulses were started shortly after admission. C3NeF and anti-factor H antibody tests were negative. Serum factor H and I levels were normal as well as factor H activity. Screening for mutation in the factor H gene revealed the H402 allele variant. Clinical remission, defined as normalization in renal function and in the activity levels of the complement AP, was noted at one month post-presentation and throughout the follow-up. A repeat renal biopsy showed the disappearance of crescent formation, whereas electron microscopy revealed no regression in dense transformation of the lamina densa. In summary, our patient was successfully treated with immunosuppressant and PE. The absence of known factors associated with DDD suggests that, in this particular case, other regulatory mechanisms of complement AP might have been involved in the disease process.

Long-term renal function following bone marrow transplantation.

Renal function, evaluated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), was investigated in 187 pediatric patients who underwent allogeneic (n=169) or autologous bone marrow transplantation (BMT). Allogeneic BMT patients were divided into three groups: hematological malignancies, aplastic anemia and non-malignant diseases, whereas autologous patients constituted a fourth group. A total of 64% received total body irradiation (TBI) as conditioning therapy, and 50 healthy children served as controls. GFR and ERPF were normal before transplantation. After 1 year, both GFR and ERPF were significantly reduced. GFR had recovered slightly after 3 years and remained stable thereafter. Recovery in ERPF was not apparent. Renal impairment was found in 41% of patients at 1 year, in 31% at 3 years and in 11% 7 years after BMT. Patients with hematological malignancies had lower GFRs than patients with non-malignant diseases at all time points. The most important risk factor as regards chronic renal impairment was TBI. Type of donor, cyclophosphamide (CY), or acute graft-versus-host disease (GVHD) did not seem to contribute to the development of chronic renal impairment. We suggest that tests of renal function should be included in long-term followup after BMT.

The course of diabetic glomerulopathy in patients with type I diabetes: a 6-year follow-up with serial biopsies.

Diabetic nephropathy is a severe complication and few studies have described the early morphological changes over time. Two kidney biopsies were performed, within a 6-year interval, in 29 primarily normoalbuminuric patients, aged 24 years at the second biopsy. These were examined with light and electron microscopy. Glomerular filtration rate, and effective renal plasma flow were determined with inulin and para-aminohippurate clearances. Urinary albumin excretion rate and the 24 ambulatory blood pressure were determined. Ten patients had developed microalbuminuria and/or hypertension; of these, six were treated with antihypertensive medication for 2 years or more. Significant increases were found in night time diastolic blood pressure and decreases in systolic and diastolic dipping. The glomerular volume, mesangial volume, mesangial matrix volume fraction and foot process width increased significantly. The group that was treated later for complications had the worst long-term metabolic control, thicker basement membranes and larger mesangial matrix and volume at the first biopsy, than the persistent normoalbuminuric group. During the follow-up, the untreated group with complications and the persistent normoalbuminuric group showed an increase in morphological parameters, whereas no progression occurred in the treated patients who also improved their metabolic control. In conclusion, the morphological parameters deteriorated in the normoalbuminuric patients and in those with complications, but were unchanged in the small antihypertensive-treated group with improved metabolic control.

Renal function before and long after liver transplantation in children.

BACKGROUND: Renal dysfunction occurs in children with liver diseases and renal function is often further impaired after orthotopic liver transplantation (OLT). Inaccurate methods of determining renal function are used in many cases. We studied renal function with accurate methods before and repeatedly after OLT to analyze the effect of the underlying diseases, hypertension, and the immunosuppressive agents. METHODS: A total of 46 children were studied both before and annually after OLT with clearances of inulin and paraaminohippuric acid to determine the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). The clearance of inulin was also compared with the formula creatinine clearance. RESULTS: GFR and ERPF decreased from before to after OLT and decreased further during the first years after OLT. Patients with extrahepatic biliary atresia and with tumours showed higher GFR 1 year after OLT than those with metabolic and miscellaneous disorders. No significant change in GFR of individual patients occurred from the first to the last values determined at around 1 and 6 years after OLT. No difference in renal function was seen during the first years between patients treated with cyclosporine as compared to those treated with tacrolimus, but 4 years after OLT, the GFR was higher in the tacrolimus-treated patients. Patients on antihypertensive agents had lower GFR than the normotensive ones. There was no agreement between GFR, determined by clearance of inulin, and that calculated on the basis of serum creatinine and the height of the patients. CONCLUSIONS: Renal function is reduced by OLT and decreases further during the first years after OLT. Patients with metabolic disorders and those on antihypertensive treatment have the lowest GFR. Determination of GFR by the formula creatinine clearance is inaccurate in children after liver transplantation.

Ambulatory blood pressure and heart rate in relation to kidney structure and metabolic control in adolescents with Type I diabetes.

AIMS/HYPOTHESIS: To evaluate the relationship between metabolic control, kidney function, ambulatory blood pressure and renal morphology in normoalbuminuric adolescents with Type I (insulin-dependent) diabetes mellitus. METHODS: Metabolic control, clearance of inulin and para-amino hippuric acid, 24 h ambulatory blood pressure and renal biopsies were studied in 41 patients who were 17.8 +/- 0.5 (SEM) years of age and 10.7 +/- 0.5 years after onset of diabetes. RESULTS: Glomerular filtration rate and filtration fraction were higher in diabetic patients than in healthy control subjects. At least one third of the patients had systolic and nocturnal diastolic blood pressures above the 90th centile. Basement membrane thickness was 512 +/- 17 nm, volume fraction of mesangial matrix 10.7 +/- 0.3% and foot process width 415 +/- 6 nm. Nocturnal mean arterial blood pressure, adjusted for body height and gender, correlated directly to the basement membrane thickness, the volume fraction of mesangial matrix and the foot process width. Multiple regression analysis showed that HbA1c, nocturnal heart rate and body height account for 44% of the variations in blood pressure. HbA1c, nocturnal heart rate and body height explained 57% of the variation in basal membrane thickness, and HbA1c, nocturnal heart rate and duration of diabetes explained 43% of Vv(matrix/glom). Actual renal function or urinary albumin excretion rate had no effect. CONCLUSION/INTERPRETATION: Nocturnal heart rate and nocturnal blood pressure, especially the mean arterial blood pressure, seem to be related to glomerulopathy changes in patients in whom persistent microalbuminuria has not yet developed. These findings suggest that a disturbance in sympathovagal balance could have a pathogenic effect.

Long-term follow-up of renal function in recipients and donors following pediatric kidney transplantation.

Of 125 children undergoing kidney transplantation (tx), 87 received their grafts from living donors. Renal function of recipients (R) and donors (D) was assessed by glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) determined by clearances of inulin and para-aminohippuric acid. Rs were investigated yearly and Ds on alternate years. Within 5 months of tx, absolute GFR and ERPF (ml/min) were significantly lower in R than in D, and the differences in absolute GFR and ERPF between D and R were directly related to the difference in body surface area (BSA) between the two subjects. R and D pairs were repeatedly followed for 4, 6, and 8 years and the absolute GFR of R did not change during follow-up, while relative GFR decreased. Relative GFR decreased most in R, with the greatest difference in BSA between D and R at tx. In the donors, however, both absolute and relative GFR increased significantly up to 8 years. In conclusion, renal function of the two kidneys from the donor, i.e., the grafted kidney in the R and the single native kidney of the D, differed. The native kidney showed a capacity to increase its absolute and relative function with time. The grafted kidney, however, did not show an increase in absolute GFR, resulting in decrease in relative GFR, and the greater difference in BSA between D and R at tx, the greater fall in relative GFR of the R.

Renal transplantation in children: psychological and donation-related aspects from the parental perspective.

Parent(s) accompanying their 18 children to the annual medical follow-up after renal transplantation were interviewed by a child psychiatric social worker. Thirteen of the children had received their grafts from one of their parents, two from other relatives, and three from cadaveric donors. The aims of this interview were to study the decision-making process regarding donation, and the consequences, reflections, and psychological reactions from the parental perspective. Although most parents reported improved psychosocial functioning of the family, many parents also reported significant psychological distress, in many cases complicated by unemployment related to the care of the child. Most parent donors reported that the relationship with their child had improved. For most parents, the decision about the donation seemed to have been a matter of course. However, the process may have induced suffering in those parents who had felt obliged to donate. Thus, questions regarding donation must be approached in a professional and non-judgmental manner when parents are informed about the preconditions of transplantation. The present results indicate a need of psychosocial support for all families during the transplantation process. Therefore, a psychologist and a social worker have been included in the pediatric nephrology team at our unit. The donors also require further information concerning the operative details as well as in regard to the post-operative pain.

Glomerular function and morphology in puromycin aminonucleoside nephropathy in rats.

BACKGROUND: The most characteristic manifestation of minimal-change nephropathy is podocyte cell process broadening. In a previous study in children from our unit, we found an inverse correlation between foot process width, glomerular filtration rate (GFR), and filtration fraction. The aim of the present study was to determine whether this relationship also existed in the puromycin aminonucleoside (PAN) experimental model. METHODS: Sixteen Munich-Wistar-Frömter male rats initially weighing median 247 g (range 171-286) were used. Four rats served as controls. The other 12 rats were divided into three groups receiving daily subcutaneous injections of 1, 1.67, and 2.5 mg PAN/100 g body weight respectively, for 6 days. GFR was determined by clearance of inulin and the fractional urine albumin excretion was measured. Standard stereological methods were used to estimate the glomerular volume, the mean foot process width and the length density of slit pores. RESULTS: GFR decreased with increasing PAN doses. The glomerular volume was increased in the group receiving the lowest PAN dose, while it was decreased in the group with the highest PAN dose, compared with controls. The fractional albumin excretion and the foot process width increased and the total slit pore length decreased with increasing doses of PAN. GFR correlated directly with the glomerular volume as did the foot process width with the fractional albumin excretion. The foot process width correlated inversely with the glomerular volume as did the glomerular volume with the fractional albumin excretion, and GFR with foot process width. CONCLUSIONS: The decreased GFR found in the nephrotic rats was inversely related to foot process width and directly related to glomerular volume, confirming our previous results in children in an early stage of the nephrotic syndrome.

Influence of serum albumin on renal function in nephrotic syndrome.

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), determined by the clearances of inulin and para-aminohippuric acid, were evaluated in 119 children with different types of nephrotic syndrome and in different stages: the nephrotic stage (serum albumin < 25 g/l), recovery stage (25-35 g/l), and remission (> 35 g/l). GFR in the nephrotic stage was significantly lower than in remission and in controls, and was lowest at onset of the disease (84 +/- 6, 111 +/- 4, and 119 +/- 2 ml/min per 1.73 m2). ERPF was higher in the nephrotic stage than in recovery, especially in children with histological lesions. Thus the filtration fraction (FF) was greatly decreased in the nephrotic stage. In patients investigated both in the nephrotic and the remission phase, GFR and FF increased significantly. There was a direct correlation between the serum albumin concentration and FF and an inverse correlation between mean arterial pressure (MAP) and GFR and FF in all patients, a direct correlation between the serum albumin concentration and GFR in minimal change nephrotic syndrome patients, and an inverse correlation between ERPF and serum albumin in children with histological lesions. In conclusion, GFR and FF were decreased and ERPF increased in the nephrotic stage, normalizing in remission. The low GFR in the nephrotic stage was thus not dependent on hypoperfusion. We suggest that the low GFR is dependent on a very low ultrafiltration coefficient. The direct correlation between GFR and serum albumin and the indirect correlation between GFR and MAP suggest compensatory mechanisms that increase the ultrafiltration pressure to counteract the severely reduced ultrafiltration coefficient.

Kidney morphological changes in relation to long-term renal function and metabolic control in adolescents with IDDM.

For the past 10-15 years all the children at our unit with insulin-dependent diabetes mellitus have been repeatedly followed-up with renal function tests. Renal biopsy, examined by light and electron microscopy, was included in the follow-up of 36 adolescents and young adults, aged 13-25 years, with a disease duration of 7-19 years. All subjects had undergone at least three renal function tests before biopsy and none had persistent microalbuminuria. Renal function was evaluated as glomerular filtration rate and effective renal plasma flow determined by clearances of inulin and para-amino hippuric acid. Glomerular filtration rate and filtration fraction were increased before and at the time of the biopsy. Glomerular basement membrane thickness (331-858 nm) and mesangial matrix volume fraction (7.4-17.1%) were increased. Long-term hyperfiltration and hyperperfusion before biopsy correlated inversely with mean glomerular volume. Increased filtration fraction before the biopsy correlated directly with mean of all HbA1c (r = 0.485, p < 0.01) and both variables correlated directly with mesangial matrix volume fraction, basement membrane thickness and structural index (r = 0.433, p < 0.01 and r = 0.626, p < 0.001, respectively). Urinary albumin excretion rate correlated directly with foot process width (r = 0.645, p < 0.001). By multiple regression analysis the most important variable for the increase in basal membrane thickness was the metabolic control while the mean of previous filtration fraction was most important for the increase in mesangial matrix volume. In conclusion, although none of the patients showed constant microalbuminuria, early diabetic structural changes were evident with basal membrane thickening and increased mesangial matrix volume. The structural changes related to long-standing hyperfiltration and poor metabolic control.

To be or not to be a living donor: questionnaire to parents of children who have undergone renal transplantation.

BACKGROUND: Between 1981 and 1994, 67 transplantations were performed in 59 children below 16 years of age at Huddinge University Hospital. In most of the cases, one of the parents was the donor. The aim of this study was to evaluate how the transplantation influenced the parents. METHODS: One hundred sixteen individual questionnaires were sent out to the donor parents and to the parents who for different reasons had not been donors. Of special interest was to investigate the emotional reactions, the social consequences, the relationship to the child, and the parents' attitudes toward donation. RESULTS: Thirty-five donors and 41 nondonors replied. The majority of both donors and nondonors were satisfied with the medical information. The nondonors expressed more stress and anxiety before the transplantation. More than half of the donors experienced the operation as more painful than they had expected. Despite this fact, the nondonors showed significantly more psychosomatic/psychiatric symptoms than the donors after the operation. The donors reported an improved relation to the recipient child after the transplantation to a greater extent than the nondonors. Half of the donors reported an improved self-esteem after the donation. None of the donors regretted their donation and all of them would do the same again. CONCLUSIONS: This study indicates that ethical and psychological risks in parental kidney donation should not be regarded as a major obstacle. However, irrespective of the parents being a donor or not, they wanted more psychosocial support both before, during, and after the transplantation.

Influence of donor and recipient ages and sex on graft function after pediatric renal transplantation.

BACKGROUND: Adult donor grafts adapt to the smaller size of the child recipient by reducing their absolute glomerular filtration rate (GFR) (ml/min). The question arises whether these grafts can increase the absolute GFR when the child recipient grows or whether a child donor graft can better increase its function. The aim of this study was to evaluate the influence of donor and recipient ages and sex on renal function. METHODS: Eighty-five children and adolescents, aged 0.4-20.5 years at transplantation, were monitored annually, by GFR and effective renal plasma flow (ERPF), determined by clearances of inulin and para-aminohippuric acid. The patients received 90 grafts from donors aged 3-67 years. Follow-up time was around 5 years. RESULTS: Absolute GFR and ERPF (ml/min) of grafts from donors <20 years of age (all cadaveric donor grafts) increased during follow-up, resulting in a constant relative GFR and ERPF (ml/min/1.73 m2), whereas absolute GFR and ERPF of grafts from donors >20 years of age remained constant during follow-up, resulting in a significant decrease in relative values. Relative GFR and ERPF fell during follow-up in young recipients (<12 years of age), but remained constant in older recipients (>12 years). Donor and recipient sex did not influence renal function. CONCLUSIONS: Child donor grafts seem better able to increase their function with the growth of the child recipient than adult grafts. However, the limited access to pediatric grafts and the fact that pediatric cadaveric grafts might involve technical problems in connection with grafting restrict their use.

Renal functional reserve in transplanted and native single kidneys of children and adults.

Renal functional reserve (RFR) after an oral protein load was evaluated in 36 cyclosporine-treated children following kidney transplantation (Tx), in 15 kidney donors (Don), and in 15 children with single kidneys (Nx/Ag). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by clearances of inulin (and creatinine) and para-aminohippurate during water diuresis. Baseline and stimulated GFR and ERPF were determined and RFR was calculated as the difference between stimulated and baseline values. Baseline GFR and ERPF in Tx were lower than in Don and Nx/Ag. Both GFR and ERPF increased significantly in all groups from baseline to stimulated values. RFR GFR was 23% +/- 3%, 20% +/- 3% and 15% +/- 3% in Tx, Don, and Nx/Ag and RFR ERPF 35% +/- 4% in Tx, which was significantly higher than 20% +/- 4% and 15% +/- 3% in the two other groups respectively. Stimulated GFR and ERPF in Tx correlated with kidney length. No differences were seen in recipient-donor pairs, except for higher fractional increases of ERPF in recipients. There was no correlation between RFR measured by clearance of creatinine and clearance of inulin. In conclusion, cyclosporine-treated children following renal Tx were found to have a renal reserve capacity.

Comparative evaluation of iohexol and inulin clearance for glomerular filtration rate determinations.

We evaluated iohexol as a filtration marker in 150 children. The clearance of iohexol was compared with that of inulin or with a formula clearance. The single-sample clearance of iohexol showed a good correlation with the clearance of inulin (r = 0.834). The clearance of iohexol correlated well (r = 0.672) with the formula clearance. The optimal blood sampling time for iohexol clearance determinations appears to be between 120 and 180 min after injection, at least in patients with relatively normal filtration rates. We conclude that iohexol clearance is an accurate method of determining the glomerular filtration rate in clinical practice.

Potter sequence and consanguinity--a case report.

The first child of first-cousin parents had Potter sequence, including rudimentary, dysplastic kidneys and pulmonary hypoplasia. The girl died after 5 h. During the next pregnancy, early fetal ultrasound was normal. In the 33rd week, however, ultrasound revealed oligohydramniosis and reduced renal size. After 40 weeks of gestation a healthy girl of normal weight without any stigmata was born. Her pulmonary function and X-ray were normal. Renal ultrasound demonstrated small kidneys with high echogenicity. There was a transient renal insufficiency with a peak serum creatinine of 160 mumol/l. At 5 months of age the infant still has an increased serum creatinine concentration of 57 mumol/l and an inulin clearance of 29 ml/min per 1.73 m2. In this case there is a possibility of an autosomal recessive inheritance.

Ten years' experience of renal transplantation in children in the cyclosporine era.

Sixty renal transplantations were performed in 53 children, 0.4-16.0 years of age during the last 10 years. Fifty-five percent of the children were < or = 7 years at transplantation and 23% were < or = 2 years. Congenital nephropathies were the primary disease in 79%. Preemptive transplantation was performed in 24 first transplantations. Forty-two grafts came from living related donors and 18 came from cadaveric donors. The 1- and 5-year patient survival rates in the 0- to 7.0-year age group were 83% and 83%, respectively, and in the 7.1- to 16.0-year age group, 100% and 93%. The 1- and 5-year graft survival rates were 77% and 77% and 90% and 74% in the two groups, respectively. In children < or = 2 years old at transplantation, the 1- and 5-year patient and graft survival rates were the same, 86% and 86% in living related donors recipients, whereas they were 40% and 40% in cadaveric donors recipients. Six patients died, 3 with functioning grafts. An additional 7 grafts were lost in 6 patients, all of whom were subsequently retransplanted. The median height SD scores at transplantation was -2.98 SD in children with congenital diseases and -0.48 SD in children with acquired diseases. The median height SD scores of the 22 children followed for 3 years after transplantation was -1.06 SD. It is concluded that the survival rates obtained are satisfactory, despite the fact that the majority of the children were transplanted at a comparatively young age because of a high frequency of congenital renal disorders.

Follow-up of renal function and urinary protein excretion in childhood IgA nephropathy.

Renal haemodynamics and urinary protein excretion (UPE) were investigated in 36 patients with IgA nephropathy more than 3 years after renal biopsy (mean interval 6.3 +/- 0.5 years). At follow-up, 39% of patients had a reduced glomerular filtration rate (GFR) and 11% endstage renal failure. Twenty-five percent had albuminuria, and a further 25% microalbuminuria. All albuminuric patients had GFRs below the mean, and 78% of the albuminurics had a reduced GFR. However, non-albuminurics also had decreased GFRs and GFR tended to fall with the duration of the disease in this group of patients. On comparing the histological changes in the biopsies with haemodynamic and UPE studies performed 6 years later, we found significant correlations between the extent of segmental glomerular sclerosis and GFR, effective renal plasma flow, urinary albumin and IgG excretion, respectively. Histological grading correlated with the same variables. Of the 4 uraemic patients, 2 were nephrotic at presentation, while the other 2 had a nephritic onset of disease and later developed heavy proteinuria. Three of their biopsies showed > or = 10% segmental glomerulosclerosis. Juvenile IgA nephropathy is not a harmless disease. Our results indicate that these children should be carefully monitored with adequate GFR measurements and urine protein analyses.

Long-term followup of renal morphology and function in children with recurrent pyelonephritis.

Renal morphology and function were evaluated in 161 children with recurrent pyelonephritis with or without vesicoureteral reflux and with or without scarred or small kidneys. The patients were followed for 1 to 21 years. Renal function was determined by glomerular filtration rate and effective renal plasma flow by clearances of inulin and paraaminohippuric acid. Of 105 children with normal kidneys originally small or scarred kidneys developed in 37, of whom 22 had grade III or greater vesicoureteral reflux, while small kidneys developed in 13 of 29 children with renal scarring originally. Of the 37 children with normal kidneys originally renal parenchymal scarring developed in 14 after the age of 4 to 5 years. Glomerular filtration rate was already < -2 standard deviations of that of controls in 51% of the patients at the first and in 53% at the last investigation of renal function. Of these patients with a glomerular filtration rate of < -2 standard deviations 69% had small or parenchymally reduced kidneys most of whom had the first pyelonephritis episode before age 3 years. Patients with small kidneys had a lower glomerular filtration rate than those with normal sized kidneys, whether scarred or not. The low glomerular filtration rate and its subsequent further reduction were related to kidney size and not to the presence or degree of vesicoureteral reflux. However, in individual patients the rate of functional deterioration could not be predicted from the radiological findings. Patients with bilateral small kidneys seemed to show the greatest decrease in glomerular filtration rate during followup as did those with grade III or greater reflux undergoing surgery bilaterally and those patients also had a lower glomerular filtration rate at the last investigation compared to patients not undergoing surgery. In conclusion, renal functional damage seems to occur early in the course of the disease and seems to be related to kidney size but there is a further slow progression with reduction in renal function which occurs, although this is difficult to predict from the radiological changes in individual patients. Therefore, patients with recurrent pyelonephritis should be followed regularly by glomerular filtration rate determination using an accurate method.