This includes people who are:. A range of experts, including a task force of the National Kidney Foundation and American Society of Nephrology , have identified racism and inequities in healthcare as factors that help explain the increased risk.

If you have diabetes, there are several steps you can take to help lower your risk of diabetic kidney disease. If you have diabetes, your doctor will screen you for kidney disease each year by measuring GFR and urine albumin levels.

This yearly screening can help detect kidney disease early and prevent additional damage from occurring. There are many places to find resources and support , such as:.

Additionally, you can find more information about kidney disease by checking out the websites for the National Kidney Foundation or the American Kidney Fund.

People with diabetes are at an increased risk of developing kidney disease. By taking steps to manage your diabetes and live a health-promoting lifestyle, you can reduce your risk.

A GFR test is one way for your doctor to assess your kidney function. Having a lower-than-normal GFR can indicate kidney disease or even kidney failure.

If you have diabetes, your doctor will check your kidney function yearly by testing and measuring your GFR and urine albumin levels. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available.

VIEW ALL HISTORY. Discover the link between type 2 diabetes and kidney disease, the leading cause of kidney failure in the United States. Learn preventive steps you can…. Regularly screening your kidney health is a part of actively managing diabetes. It's the most effective way to detect kidney damage early and improve….

One of the most common electrolyte imbalances experienced by people with kidney disease, which can lead to muscle weakness, pain, or even paralysis….

Nephropathy is one of the more serious, potentially life-threatening complications of diabetes. But there are steps you can take to lower your risk of…. High protein levels in the urine are known as proteinuria. Discover 11…. A urine protein test measures the amount of protein in urine.

This test can be used to diagnose a kidney condition or see if a treatment is working. A Quiz for Teens Are You a Workaholic? How Well Do You Sleep? Health Conditions Discover Plan Connect. Get Motivated Cardio Strength Training Yoga Rest and Recover Holistic Fitness Exercise Library Fitness News Your Fitness Toolkit.

About Glomerular Filtration Rate GFR and Diabetic Kidney Disease. Medically reviewed by Marina Basina, M. About GFR What's normal? Abnormal GFR Diabetes and kidney disease Risk factors Prevention Resources Summary.

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Read more about our vetting process. Was this helpful? What is a glomerular filtration rate GFR test? Average glomerular filtration rate by age According to the National Kidney Foundation , the average GFR results by age are as follows: Ages 20 to Ages 30 to Ages 40 to 99 Ages 50 to 93 Ages 60 to 85 Ages 70 and older: What does an abnormal GFR mean?

Can low GFR be reversed? Steps you can take include: managing your diabetes to keep blood sugar at target levels preventing or treating high blood pressure eating a diet high in fresh vegetables and low in processed foods and salt getting regular, moderate exercise Before making any major changes to your lifestyle, be sure to talk with your doctor.

How does diabetes increase the risk of kidney disease? What are the risk factors for diabetic kidney disease? If you have diabetes, what can you do to prevent kidney disease? Resources and support. The bottom line.

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Medically reviewed by Kelly Wood, MD. How to Screen for Diabetes-Related Nephropathy. What Is Diabetic Nephropathy Hyperkalemia?

It is also a good indicator of diabetes diagnosis, efficacy evaluation, the observation of treatment compliance, and prognosis judgment and plays an important role in evaluating the occurrence and development of various diabetes complications.

However, there are few reports on the relationship between changes in HbA 1c level and eGFR in T2D patients. Accordingly, we studied the association between short-term changes in eGFR and HbA 1c in patients with T2D during a month follow-up period.

This was an observational, multicenter, retrospective study based on medical records included in the Diabetes Sharecare Information System DSIS of Ruijing diabetes chain hospitals RDCHs , five primary care medical institutes located in the cities of Beijing, Taiyuan, Chengdu, Harbin, and Lanzhou.

Only patients who provided oral consent for inclusion in the study were allowed to be registered. RDCHs began using DSIS in All data were aggregated for each person after registration baseline and during each follow-up visit. The Declaration of Helsinki guidelines were followed while conducting this study.

The research was approved by the Ethics Committee of Beijing Ruijing Diabetes Hospital. Due to the nature of the study i. The inclusion period lasted from January 27, , to April 26, The final cohort comprised 2, adults with T2D Figure 1. Figure 1 Flowchart and sample size of participants for the final analyses.

T2D, type 2 diabetes; eGFR, estimated glomerular filtration rate; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; UACR, urinary albumin-to-creatinine ratio.

The HbA 1c measurements were tested with high-performance liquid chromatography using HA ARKAY, Inc. Biochemical parameters, including serum creatinine, low-density lipoprotein cholesterol LDL-C , and urinary albumin and creatinine were tested by automatic biochemical analyzers using a TBAFR Toshiba, Beijing, China , CS DIRUI, Changchun, China and BS Mindray, Shenzhen, China in regular quality control and meeting the local internal quality control standards.

Clinical measurements of HbA 1c and serum creatinine were obtained from the laboratory database from the time of cohort entry to the second if no third record or third follow-up exam. Medication information was obtained on the registration date and during follow-up visits.

Treatment for hyperglycemia was categorized into two groups, i. Patient characteristics were summarized using mean and standard deviation and median and interquartile range or numbers percentages.

Interactions with HbA 1c changes were determined. All analyses were performed using the SPSS Statistics The final analytic cohort comprised 2, individuals with T2D, with a median age at entry of The proportion of patients that had a history of hypertension, dyslipidemia, diabetic retinopathy DR , or DKD was Table 1 Demographic and clinical characteristics for the overall study population.

Table 3 Demographic and clinical characteristics for the five different eGFR change groups. We evaluated the factors associated with the average eGFR changes. The HbA 1c reduction played an important role in the eGFR decrease in subjects with hyperfiltration.

Figure 2 Trend of estimated glomerular filtration rate eGFR change in different HbA 1c decrease A and increase B groups.

Table 4 Comparison of mean eGFR change in the different HbA 1c decrease groups. The eGFR is a marker used to evaluate renal function and to predict the risk for ESRD and renal death in diabetes cases, whereas the implication of creatinine-based eGFR is limited to hyperglycemia status.

Additionally, HbA 1c was positively associated with eGFR, whether independently or together with fasting plasma glucose FPG , in participants with prediabetes and was associated with significantly increased odds ratios ORs of hyperfiltration 21 , It was also demonstrated that eGFR equations were less accurate in the diabetic group than in the non-diabetic group, and HbA 1c was an independent factor associated with the accuracy of eGFR equations Several patients with T2D experienced eGFR FD or MD during the median 8-month follow-up.

From group FI to FD, baseline HbA 1c level, HbA 1c reduction range, and the age-adjusted prevalence of hyperfiltration increased gradually.

Patients with FD had the highest baseline HbA 1c level, HbA 1c reduction, and a prevalence of hyperfiltration as high as This may be due to the HbA 1c reduction itself, but not as a result of hyperfiltration, since the association remained significant even after adjusting for the presence of hyperfiltration.

This was not the case at first sight. Existing research demonstrated HbA 1c reduction after a few months to be associated with a significant reduction in eGFR, and the correlation could be extended to both types of diabetes and more advanced stages of renal impairment.

In day-to-day clinical practice, the prediction of GFR becomes crucial when renal function declines. We note here that eGFR and its estimations would be significantly higher in poorly controlled patients. There may be concerns about whether a decrease in eGFR indicates the decline of renal function, since the link between acute intensive glycemic control and acute neuropathies or DR progression is described in the literature 25 — The neuropathies experienced by patients were acute, severe but reversible, and did not occur as a consequence of chronic hyperglycemia.

The most important factors for the early worsening of DR were a higher HbA 1c level at screening and a reduction in this level during the first 6 months of treatment However, we cannot deny the long-term benefits of blood glucose control.

The retinal morphology improved during the following years, and intensive glycemic control continued to reduce DR progression 25 , 27 , A transient decrease in eGFR during the intervention period and its return to near the baseline level at weeks with SGLT-2i treatment indicated possible similar pathophysiological mechanisms and the development of a process for HbA 1c reduction 31 , A threshold for HbA 1c levels related to the risk of complications was observed.

Above the threshold of 6. The largest eGFR decline trend, along with HbA 1c reduction, was found in patients with hyperfiltration. The age-adjusted prevalence of hyperfiltration in this study was higher than that in a previous report The reason for this difference may have resulted from the different GFR measurement methods, definition criteria, study population, and HbA 1c levels 19 , It was found that a more considerable reduction in eGFR at 6 months significantly predicted a slower subsequent decline, and the amelioration of hyperfiltration was significantly associated with a slower long-term eGFR decline on follow-up Patients with hyperfiltration may benefit from an eGFR decline to the normal range.

Thus, caution is advised when interpreting eGFR before reaching adequate glycemic control and the amelioration of hyperfiltration, even in patients with long-term diabetes duration.

Moreover, since eGFR equations were considered less accurate in patients with diabetes, regardless of using either the CKD-EPI or MDRD equations, eGFR changes and their response to treatment should be monitored better and regularly alongside HbA 1c.

This study identified the association between short-term changes in eGFR and HbA 1c in patients with T2D during the month follow-up period. Some patients with T2D experienced eGFR FD or MD during the median 8-month follow-up period.

Since a downward trend in eGFR change was demonstrated alongside an HbA 1c reduction, regardless of the UACR stage and diabetes duration independent of hyperfiltration, sustained monitoring and the cautious interpretation of HbA 1c and eGFR changes are required in clinical practice.

We do not know whether the rapid eGFR decline associated with an HbA 1c reduction in this analysis will partly recover in future follow-ups, which requires further observation. A weakness of this study concerns its retrospective nature. Thus, the study findings are hypothesis-generated and require further testing.

The major strengths of the study were that it included a large study population and demonstrated an association between HbA 1c changes and short-term eGFR changes in populations with T2D; furthermore, all subjects were prospectively monitored using gold-standard procedures.

The results may thus present extensive external validity. Further inquiries can be directed to the corresponding author. The studies involving human participants were reviewed and approved by the Ethics Committee of Beijing Ruijing Diabetes Hospital.

Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements. LA and JL conceived and designed the study. LA analyzed the data and drafted the article. All authors contributed to data collection, critically reviewed the article, and approved the final version to be published.

This work was supported by the Beijing Fengtai District health system project No. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. We would like to express our gratitude to all those who helped us during the writing of this article.

Diabetes Atlas Group IDF. Update of Mortality Attributable to Diabetes for the IDF Diabetes Atlas: Estimates for the Year Diabetes Res ClinPract 3 —5. doi: CrossRef Full Text Google Scholar. Yu Y, Lin Q, Ye D, Wang Y, He B, Li Y, et al.

Neutrophil Count as a Reliable Marker for Diabetic Kidney Disease in Autoimmune Diabetes. BMC EndocrDisord 20 1 Jin D, Huang WJ, Meng X, Yang F, Bao Q, Zhang MZ, et al.

Chinese Herbal Medicine Tangshen Formula Treatment for Type 2 Diabetic Kidney Disease in the Early Stage: Study Protocol for a Randomized Controlled Trial. Trials 20 1 PubMed Abstract CrossRef Full Text Google Scholar.

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The Microvascular Complications Group of Chinese Diabetes Association. Chinese Clinical Practice Guideline of Diabetic Kidney Disease.

Chin J Diabetes Mellitus 11 1 — Google Scholar. National Kidney Foundation. KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Chapter 1: Definition and classification of CKD.

Kidney Intsuppl — National eGFR project cooperation group Collaboration. Modification and Evaluation of MDRD Estimating Equation for Chinese Patients With Chronic Kidney Disease.

Chin J Nephrol 22 10 — Espinel E, Agraz I, Ibernon M, Ramos N, Fort J, Serón D, et al. Renal Biopsy in Type 2 Diabetic Patients. J Clin Med — Krolewski AS, Skupien J, Rossing P, Warram JH. Fast Renal Decline to End-Stage Renal Disease: An Unrecognized Feature of Nephropathy in Diabetes.

Kidney Int 91 6 — Skupien J, Warram JH, Smiles AM, Niewczas MA, Gohda T, Pezzolesi MG, et al. The Early Decline in Renal Function in Patients With Type 1 Diabetes and Proteinuria Predicts the Risk of End-Stage Renal Disease. Kidney Int 82 5 —

She came again in August presented with apparent nephrotic syndrome with grossly edematous lower limb with ascites and poorly controlled blood pressure to the emergency department. Urgent renal doppler ultrasound showed normal size kidneys, no evidence of obstructive uropathy or renal vein thrombosis.

There are also features of interstitial nephritis seen. Diabetic nephropathy Tervaert Class IV with moderate hypertensive vascular changes and interstitial nephritis Fig.

She was counselled on long term renal replacement therapy and she has been dialysis dependant since then. B, 41 Malay male who was newly diagnosed T2DM and Hypertension about a year ago in a local private hospital. His initial presentation was nephrotic syndrome with normal renal function.

Patient was however non-compliance to his medications and went to seek traditional medications and also alternative medications.

On examination he has bilateral pleural effusion, pedal edema and ascites. B was admitted again with gross bilateral lower limb swelling and right forearm abscess in July During this admission he was treated as acute on chronic kidney disease secondary to right forearm abscess.

His renal function did not recover despite antibiotic and dialysis support. Renal ultrasound was normal. Renal biopsy was performed and it was reported as diabetic nephropathy Tervaert Class III with moderate to severe hypertensive vascular changes and interstitial nephritis Fig.

Patient became dialysis dependant and currently is on hemodialysis as his mode of long term RRT. Madam C, year-old Malay lady, diagnosed with T2DM since year-old and hypertension at the age of year-old. She was previously under health clinic follow up but was not compliance to her medications including oral hypoglycemic agents.

Her Hba1c in was She was referred to nephrology clinic in august for rapid decline in renal function and worsening pedal edema. Ultrasound kidneys showed normal kidney sizes with no obstructive uropathy.

Ophthalmology review noted bilateral extensive proliferative diabetic retinopathy. She has admitted to have tried traditional medications. She was counselled for renal biopsy in view of sudden drop in renal function and hemodialysis had to be initiated. Renal biopsy showed Diabetic nephropathy Tervaert Class III with moderate to severe hypertensive vascular changes and tubulointerstitial nephritis.

Diabetic nephropathy DN or diabetic kidney disease is characterized by its unique functional and structural changes. During the initial phase of clinically silent period, important structural changes occur.

These include glomerular basement membrane thickening, mesangial proliferation, podocyte injury, and glomerular sclerosis. These histopathologic abnormalities are noted to be presence before the onset of moderately increased albuminuria. On the other hand, functional changes include hyperfiltration, micro and macroalbuminuria, with incipient progressive proteinuria that slowly progressed into chronic kidney disease and eventually ESRD.

In a study of carried out in San Francisco outpatient dialysis units, 7. Unfortunately, the author did not provide much information about causes of the rapid declined in kidney function or any remedial step was taken. In a logistic regression model with rapid decline as the outcome, the Spanish researchers has reported that previous cardiovascular disease and higher proteinuria were the main predictors of rapid kidney decline odd ratio 1.

In the same study, the rapid decliners consisted of more diabetic patients. In the Cardiovascular Health Study done by Shlipak et al. All three patients were noted to have overt proteinuria at diagnosis. Only one patient had respectable Hba1c at 7.

However, it is important to note that the patient with better Hba1c had anemia at presentation and this may have led to a falsely low A1c reading. All patients had poorly controlled BP during follow up, and 2 patients had acute kidney injuries secondary to infections that have accelerated the renal deterioration.

Their renal biopsies showed diabetic nephropathy with chronic, severe tubulointerstitial damage and interstitial nephritis Figs. Proteinuria has long been recognized as an independent risk factor for renal function loss.

It is the cardinal feature of acute and chronic kidney disease. The presence and severity of proteinuria has been shown to be a reliable strategy to identify rapid renal decline in community-based prospective cohort study [ 7 ]. Measurement of total protein in urine is an inexpensive and well-established marker for kidney injury.

The failing kidney is characterized histologically by tubulointerstitial inflammation, tubular cell apoptosis, tubular atrophy and fibrosis, and these changes correlate with the severity of proteinuria.

Heavy tubular proteinuria also predicts a longer duration of interim dialysis support in patient with kidney injury in our population [ 8 ].

In healthy kidneys, proximal tubules epithelial cells PTEC can reclaim proteins that have managed to pass the glomerular filtration barrier via endocytosis.

The complex mechanisms of PTEC protein handling involve the much studied megalin-cubilin complex [ 9 ]. However, this process is compromised in diseased glomeruli, where excess filtration of bioactive proteins into the tubular fluid can dysregulated PTEC signaling pathways in response to protein leakage from the glomeruli.

As a consequence, there are abnormal PTEC growth, apoptosis, gene transcription and inflammatory cytokine production [ 9 ]. Traditional supplement has been known to contain various herbal compounds that are nephrotoxic to kidneys.

Aristolochic acids, anthraquinones, flavonoids, and glycosides from herbs have all been implicated for causing nephropathy. The exact pathogenesis of supplement related AKI has not been well established. Most of the time, the diagnosis is made via history of consumption of the supplement and demonstration of acute tubular necrosis and acute interstitial nephritis as per our case [ 10 ].

It has been our experience that the renal functions of patients who have heavy proteinuria tends to suffer the most when they also taking herbal compounds concurrently. Two of the patients Madam A and Mr. B have recurrent infections and needed courses of antibiotics.

None of them have received non-steroidal anti-inflammatory drugs or contrast agents. However, all of them did receive diuretics. The prescribed medicines and the rapid fluctuation in their extracellular water compositions may have inadvertently cause some degree of interstitial nephritis or pre-renal acute kidney injuries.

DN patients are the one of the most common nephropathies being referred to our instituation [ 11 ]. It was the rapid deterioration of the renal function that has prompted to perform diagnostic renal biopsies.

There are many ways to retard diabetic nephropathy progression. Current management practices advocate that the best way to reduce microvascular and macrovascular complications is by treating the sugar control to target.

In addition, as the rate of progression DN is also closely related to blood pressure control at baseline, a good blood pressure control plays an equally important role in retarding DN progression. As a matter of fact, it has been demonstrated that for DN patient with a background of hypertension, glycemic control may have little independent predictive value [ 12 ].

This is further strengthened by the findings from the United Kingdom Diabetes Prospective Study UKPDS , whereby a sustained reduction in blood pressure came out as the most important single intervention that could slow down the progression of diabetic nephropathy in both Type 1 and type 2 DM patients [ 13 ].

Achieving this target is also associated with renoprotective effects, although there may be particular advantages conferred following blockade of the renin- angiotensin system RAS [ 14 ]. Novel treatment strategies targeting different pathway, such as inflammation, fibrosis, and oxidative stress— are on-going for treatment of DN [ 15 ].

It is also important to retard the microalbuminuria as once overt proteinuria develop, it is almost difficult to retard the CKD progression.

Currently there is no one-off investigations that can distinguishing fast decliners from slow decliners. Serial measurements of serum creatinine performed in the clinic often detect late stages of the fast decliners.

The traditional end points used in clinical trials such as doubling of serum creatinine level or ESRD are not suitable to detect rapid decliners and this has hamper the effective evaluation of clinical trials in rapid decliners.

Massive interest is underway to find an effective prognostic marker that identifies decliners at a single clinical encounter. Until recently 30 biomarkers showed significant associations with rapid progression after adjusted for clinical characteristics.

Elevated serum TNF receptor 1 and 2 have shown early promise to become effective predictors of fast renal decline to ESRD in diabetic population [ 18 ]. Understanding the mechanisms underlying heavy proteinuria in T2DN that leads to rapid renal deterioration is desired to halt this undesirable event.

Future studies will include identifying bio-markers, understanding individual variation in rate of decline, designing novel treatment targets and perhaps individualizing treatment for T2DN. Chawla LS, Bellomo R, Bihorac A, Goldstein SL, Siew ED, Bagshaw SM, Bittleman D, Cruz D, Endre Z, Fitzgerald RL, Forni L, Kane-gill SL, Hoste E, Koyner J, Liu KD, Macedo E, Mehta R, Murray P, Nadim M, Ostermann M, Palevsky PM, Pannu N, Rosner M, Wald R, Zarbock A, Ronco C, Kellum JA.

These studies were approved by the committee for the Use of Human Subjects in Research of the University of Minnesota. Informed consent was obtained from all participants before each study. The patients were admitted in the general clinical research center GCRC at the University of Minnesota where renal function studies and percutaneous kidney biopsy were performed.

Blood pressure was measured by trained observers using an oscillometric automatic monitor while the patients were in the GCRC. The mean value of multiple measurements was used to calculate systolic and diastolic blood pressure.

HbA 1c was measured by high-performance liquid chromatography HPLC. Serum and urinary creatinine were measure by Jaffé reaction. AER was assessed in three h sterile urine collections by a fluorimetric immunoassay The median AER value for each patient was used for the analyses.

GFR was estimated by iothalamate clearances using four timed urine and blood collections HPLC 36 patients or by the mean of two or three h creatinine clearances, with urine carefully collected under direct supervision of the GCRC nursing staff 69 patients. Bland-Altman plots indicated no trend or deviation, and there was no significant difference between the values obtained by these two methods.

Retinopathy was assessed by fundoscopy in patients and classified as absent, background, or proliferative. Electron microscopy tissues were processed as detailed elsewhere 12 , A calibration grid was photographed with each glomerulus, and 10—20 evenly spaced micrographs were obtained at 11,× for measurement of glomerular basement membrane GBM width and for mesangial composition.

The presence of at least two nonsclerotic glomeruli per biopsy in the EM blocks was an entry criterion for this study. However, in most cases, three glomeruli were used.

Results are presented as mean ± SD. AER is presented as median and range. Values for AER were logarithmically transformed before analysis. Unpaired t tests were used to compare continuous variables between the low GFR and the normal GFR groups. Discrete variables were compared by χ 2.

A total of patients 65 women were studied. Age was HbA 1c at the time of biopsy was 8. Median AER was 7. Age, age at diabetes onset, and diabetes duration were not different between low and normal GFR patients. HbA 1c was similar in low and normal GFR patients.

AER was not different between groups. Fifty-six percent of normoalbuminuric women with proliferative retinopathy had low GFR. These relations between structural parameters and GFR were not seen among the 82 normal GFR patients.

There were no significant correlations between AER and GFR. There were no significant correlations between AER and structural variables in the low GFR group.

Long-standing type 1 diabetic patients with normal AER are still at risk of developing clinically significant nephropathy 16 , It is therefore important to identify markers of increased nephropathy risk among these patients. One possibility is to perform kidney biopsies in such patients, given that those with more advanced glomerulopathy are more likely to develop abnormalities in AER 7.

However, this is not very practical in most clinical settings. Thus, we examined whether reduced GFR can be predictive of more advanced underlying glomerular lesions. We previously reported that reduced GFR in eight normoalbuminuric long-standing type 1 diabetic women was associated with worse diabetic glomerular lesions 5.

Shortly thereafter, a small group of normoalbuminuric long-standing type 1 and type 2 diabetic largely female patients with reduced GFR was described 6. A similar prevalence of reduced GFR was reported among long-standing normoalbuminuric and normotensive type 1 diabetic patients in Brazil Reduced GFR has also been observed in normoalbuminuric type 2 diabetic patients in Denmark 19 , but the higher prevalence of hypertension among type 2 diabetic patients could have accounted for some GFR loss.

However, other investigators 20 did not encounter reduced GFR in normoalbuminuric type 1 diabetic patients. Based on this paucity of information and these conflicting results, the present study was undertaken using a much larger cohort of patients and confirmed that reduced GFR occurs among normoalbuminuric long-standing type 1 diabetic patients.

This, and the earlier studies 5 , 6 , showed a marked predominance of this phenomenon in women. Our earlier report 5 suggested that, at least in part, the sex effect could be related to the self-selection of a low protein diet among female patients, but this was not investigated in the present cohort.

As noted, a large cross-sectional study did not observe reduced GFR among normoalbuminuric type 1 diabetic patients However, diabetes duration was shorter 20 , mean of 14 years in this study versus 23 years in the present study.

Also, patients with diabetes duration as brief as 1 year were included in the former 20 versus a minimum of 10 years in the present study. Finally, patients on antihypertensive drugs were excluded from this earlier study 20 , whereas our report indicates that low GFR is much more common among normoalbuminuric patients who are on these medications.

Thus, the differences in the findings of the present and the earlier report of Hansen et al. These differences are unlikely to be explained by differences in GFR methodology.

Although inulin clearance is considered to be the gold standard for GFR estimates, iothalamate clearances are highly correlated with the inulin method Creatinine clearances with home urine collections are generally considered to provide a less precise estimate of true GFR, at least in part due to collection inaccuracies.

However, as already described, multiple supervised clinical research center creatinine clearances are highly correlated with inulin clearances 11 and show no deviation or trend in Bland-Altman analysis.

There were very strong correlations between this GFR estimate and renal structure within this group, further supporting the validity of this carefully performed measure as an indicator of underlying renal pathology. Moreover, the presence of low GFR was associated with worse diabetic glomerular lesions.

The statistical differences between the low GFR and the normal GFR normoalbuminuric groups were maintained when patients on antihypertensive medications were excluded from the analyses.

This excludes the possibility that our findings were caused by patient misclassification, i. A relatively high proportion of patients, hypertensive by current standards, was not receiving antihypertensive treatment, and only a small number of patients were on ACE inhibitors.

This is because many of these patients were studied when the definition of hypertension was different 22 and when ACE inhibitors were not available or commonly used. Studies evaluating structural-functional relations in diabetic nephropathy among patients ranging from normoalbuminuria to proteinuria demonstrate that AER, blood pressure, and GFR are strongly correlated with glomerular structure 13 , 23 , Thus, patients with worse lesions also have clinical changes of increased AER and blood pressure and reduced GFR.

The present study in long-standing normoalbuminuric type 1 diabetic patients confirms the association between GFR and glomerular structural parameters, even in patients with normal AER. Usually, diabetic patients developing diabetic nephropathy will initially present with increased AER followed by or concomitant with increased blood pressure before GFR decline occurs.

However, as confirmed here, a significant fraction of patients do not follow this pattern, as they can have reduced GFR and increased blood pressure before AER increases. Other efforts are being undertaken to identify normoalbuminuric patients at increased diabetic nephropathy risk before microalbuminuria or proteinuria develops.

Thus, Lurbe et al. In addition, we agree with the general thesis of the editorial by Ingelfinger 25 accompanying the article of Lurbe et al. Yonsei Med J 58 1 — American Diabetes Association.

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Collaborators on Trials of Lowering Glucose CONTROL Group.