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Renal complications of glycogen storage disease

Renal complications of glycogen storage disease

Age at presentation varied between birth and glycoegn years with a median of 6 months. Only three female patients have had recurrent urinary tract infections. Laurence Dubourg. Article CAS PubMed Google Scholar Rake JP, et al.


Understanding Glycogen Storage Disease Type 1b and its impacts.

Renal complications of glycogen storage disease -

In case of insufficient metabolic control, a Fanconi-like syndrome can develop, disappearing with improved therapy. Although renal disease has not been considered a problem in GSD I, recent findings indicate that especially in adult patients chronic renal disease is a common complication.

In the past gout nephropathy and renal stones were the complications mentioned. In biopsies of such patients focal glomerulosclerosis is found. This is a preview of subscription content, log in via an institution to check access.

Rent this article via DeepDyve. Institutional subscriptions. Baker L, Dahlem S, Goldfarb S, Kern EFO, Stanley CA, Egler J, Olshan JS, Heijman S Hyperfiltration and renal disease in glycogen storage disease type I.

Kidney Int — PubMed Google Scholar. Brewer ED The Fanconi syndrome: clinical disorders. In: Gonick HC, Buckalew VM Jr eds Renal tubular disorders, Marcel Dekker Inc, New York, pp — Google Scholar.

Chen YT, Coleman RA, Scheinman JL, Kolbeck PC, Sidbury JV Renal diesase in type I glycogen storage disease. N Engl J Med — Chen YT, Scheinman JI, Park HK, Coleman RA, Roe CR Amelioration of proximal renal tubular dysfunction in type I glycogen storage disease with dietary therapy.

Gierke E von Hepato-Nephromegalia glykogenica. Beitr Pathol Anat Allg Pathol — Grantham JJ, Chonko AW Renal handling of organic anions and cations; metabolism and excretion of uric acid.

In: Brenner BM, Rector FC eds The kidney, 3rd edn. WB Saunders, Philadelphia, pp — Hers HG, Hoof F van, Barsy T de Glycogen storage disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D eds The metabolic basis of inherited disease, 6th edn.

McGraw-Hill Inc, New York, pp — Access to Document net Persistent link. Cite this APA Author BIBTEX Harvard Standard RIS Vancouver Reitsma-Bierens, W. European Journal of Pediatrics , , SS Reitsma-Bierens, W. In: European Journal of Pediatrics. Reitsma-Bierens, WCC , ' Renal complications in glycogen storage disease type I ', European Journal of Pediatrics , vol.

In: European Journal of Pediatrics , Vol. Urine output was not recorded in this study and was not included in the classification of AKI. Post-LT AKI is based on changes in SCr from baseline creatinine within 7 days postoperatively [ 21 ]. Ultrasound examinations were used to determine the kidney length, measured as the maximum pole-to-pole distance along the longitudinal plane in centimeters cm.

Bilateral kidney length measured were expressed in z score as corresponding to the normal distribution within the same age group [ 22 , 23 ]. Nephromegaly is defined as falling outside 2 standard deviations SDs above the mean size by age group.

Demographic and operative variables included age, sex, and underlying etiology of liver disease, in addition to the coincident diagnosis of hepatic adenoma on histologic examination of the explanted liver.

Preoperative variables measured include PELD score, body height BH , body weight BW , body mass index BMI , serum albumin, aspartate transaminase AST , total bilirubin Bil , SCr, eGFR, fasting glucose, uric acid UA , total cholesterol Chol , and triglyceride TG levels.

Perioperative variables include intraoperative blood loss and graft-to-recipient weight ratio GRWR. Postoperative data included de novo hypertension HTN , AKI, growth development, as well as liver and renal functions, being continuously monitored every three to six months in the out-patient-clinic.

The primary outcome in this study was the dynamic long-term changes of renal function post-LT as evaluated by serum Cr, eGFR, presence of albuminuria and changes in sonographic kidney length. The pre-operative assessment included psychological examination and radiological assessment of the hepatic vasculo-biliary anatomy of both the donor and recipient with liver computed tomography CT angiography, magnetic resonance imaging and echography.

The decision to proceed to LDLT was made in weekly multidisciplinary meetings. All LDLT patients in the cohort received an initial standard triple immunosuppression regimen of cyclosporin A CyA , prednisolone, and azathioprine. Prednisolone was weaned off over one to two years, and azathioprine was discontinued at one-year post-LDLT.

When rejection occurred or pediatric patients transitioned into adulthood, CyA was switched to orally taken tacrolimus FK as an alternative calcineurin inhibitor CNI. In patients with elevated SCr during follow-up, mammalian target of rapamycin mTOR inhibitor was given in place of CNIs to preserve renal function.

The genomic DNA of all nine GSD-I patients were extracted from whole blood using the Gentra Puregene Blood Kit QIAGEN followed by manufacturer's protocol.

PCR products were then sequenced using an ABI DNA sequencer Applied Biosystems, Foster City, CA, USA. Data was collected and analyzed using IBM SPSS version 20 statistical software IBM corporation, Armonk, NY. Qualitative variables in both GSD and BA groups were expressed as frequency of events and cumulative incidence in percentage and compared using the chi-squared test.

Quantitative variables were expressed by their median with range and compared using the Mann—Whitney U test. Pre-LT and post-LT data were compared using the Wilcoxon signed-rank test.

The study included nine GSD-I patients. Using the propensity score matching model, 20 BA patients were selected for comparison Table 1. The preoperative age, sex, height, weight, PELD score, SCr level, and eGFR were comparable between both groups.

Hyperbilirubinemia serum total bilirubin 0. Intraoperative blood loss and GRWR between the two groups were similar. The histopathologic finding of adenoma exclusive to the GSD-I group, more specifically, all included patients in the group who underwent LT beyond the age of 9 age range: 9.

The median follow-up time duration was over 15 years All exons and splicing sites of the G6PC and SLC37A4 gene were screened in the nine GSD-I patients. Homozygous or compound heterozygous mutations including c.

R83H, p. HL and p. IN in the G6PC gene were found in eight of the GSD-I patients Table 2. All of these are known disease mutations of GSD-Ia. RC mutation was discovered in the SLC37A4 gene in case no. However, no other mutations in other exons and splicing sites were identified.

Fasting glucose, lactate, AST, TG, UA, and growth parameters showed overall significant improvement after LDLT in GSD-I patients; Chol and BMI showed borderline improvement. Clinical and biochemical parameters in 9 GSD patients before and after LT. a Changes in fasting glucose, b lactate, c aspartate transaminase AST , d triglyceride, e cholesterol, f uric acid, g height for age percentile, h weight for age percentile, i body mass index BMI.

P indicates the difference between values before and after LDLT. Although the overall postoperative eGFR was comparable vs. GSD-I patient No. Both patients had concurrent de novo HTN at the time of CKD diagnosis, which they were treated with anti-hypertensive drugs.

The annual eGFR of all GSD-I recipients after LDLT is shown in Table 2. Before the end of the study period, seven GSD-I patients We compared the dynamic change in mean eGFR among the GSD-I and BA recipients Fig.

The patients were categorized into three groups: Group A was the BA cohort, group B were GSD-I patients who were started on cornstarch therapy before reaching 6 years of age, and group C were GSD-I patients who were started after the age of 6. As shown in Table 1 and Fig. Similarly, according to the division based on the age when cornstarch therapy was initiated in GSD-I patients as mentioned above, group C demonstrated a higher level of ACR median ACR a Microalbuminuria in biliary atresia and GSD-I cohorts after LDLT.

b Relationship between microalbuminuria and age of starting cornstarch in GSD-I cohort. Routine pre-LDLT renal ultrasonography for GSD-I cases was only protocolized in January For the other two GSD-I recipients, No.

These changes have been graphically represented in Fig. On the other hand, surveillance renal ultrasonography also revealed findings of new renal cysts 0. Changes of bilateral kidney length before and after LDLT, expressed by Z scores.

a Left kidney length, b right kidney length. Whether correction of liver derangement prevents complications of GSD-I remains inconclusive. The liver transplant cases seem to be a good model to explore this possibility. However, such research is quite commonly- limited by the small study populations.

In addition, the progression of late complications such as nephropathy may be best observed with long-term surveillance. While LT is theorized to help maintain a healthy metabolic environment, the necessary use of immunosuppressive agents has been a source of inquiry as to whether it compound the risk of developing the sequelae that LT claims to mitigate, that is renal dysfunction.

Here, we have provided a follow-up data of up to 22 years median follow-up of 15 years , with multiple timepoints of assessment, in 9 GSD-I patients who underwent LDLT in our institution.

Our results revealed that the overall renal function, particularly with eGFR and albuminuria as quantitative measures, were not statistically different between the two groups median eGFR of GSD-I and BA: vs.

Patients with enlarged kidney in GSD-I patients may return to within normal range for age after LDLT. Chronic kidney disease is considered a major problem of GSD-I, first noted in [ 2 ]. Even after LT, some patients may progress to CKD. In the literature review by Boers et al. Given its relative rarity, limited numbers of GSD-I recipients could be included in this study, inadequate to conclude with statistically significant predictive variables for post-LT renal outcome and prognosis.

Despite the long-term follow-up of this study cohort, it may still be more prudent to defer any definitive conclusions regarding the development of renal dysfunction and continue observing them prospectively, as renal involvement has been typically observed to progress during adulthood among GSD type 1 patients [ 24 ].

Additionally, deterioration of renal function in patient No. The declining renal function after LT in patient No. For GSD-I patients receiving cornstarch therapy without LT, optimization of metabolic control with normal level of blood lactate, serum lipids, and uric acid may delay or prevent kidney damage [ 6 , 10 ].

A previous report demonstrated that albuminuria was retrospectively observed in patients who started cornstarch therapy at a later age 9. Our results were consistent with these findings; two patients No.

Although this hypothesis was based on observations, it suggests that the age of starting cornstarch therapy in GSD-I pre-school patients may be critical for renal outcomes.

Microalbuminuria is usually the first sign of glomerular damage in GSD-I patients, followed by proteinuria, systemic arterial hypertension, and renal failure [ 9 , 26 ]. The European Study on GSD-I reported that the prevalence of microalbuminuria ACR 2.

However, in our study, two of GSD-I patients No. These results imply that LT may preserve kidney function in GSD-I patients. Interestingly, post-LT arterial hypertension was also diagnosed in the two GSD-I patients with macroalbuminuria No.

Therefore, monitoring urine protein level and blood pressure may alert clinicians as to the onset or progression of renal dysfunction. When analyzing the factors affecting the long-term renal function in GSD-I patients, AKI occurrence was not associated with CKD in our results.

Although the recent evidence pointed that pediatric AKI attributed to several adverse long-term consequences, including proteinuria, hypertension, reduced eGFR, and CKD [ 28 , 29 ]. In our cohort, however, post-LT AKI was not associated with inferior renal outcomes in GSD and BA groups. The reasons might come from that LT surgery was the main etiology of AKI rather than sepsis and the full recovery of renal function in our patients, both of which were proved to be good indicators of AKI prognosis [ 28 , 29 , 30 ].

Liver transplantation provides a healthy liver graft to maintain a normal metabolic environment, however, the side effect of immunosuppression poses a risk of CNI related nephrotoxicity [ 31 , 32 ].

Usually, immunosuppression is tapered gradually after transplant surgery when the risk of rejection decreases, and then GFR increases accordingly. Studies by Berg et al. and Arora-Gupta et al. reported that GFR was reduced during the first year after LT [ 31 , 32 ], which is consistent with our results Fig.

With reduction in immunosuppression therapy to a lower dosage one year after LT, eGFR increased and subsequently stabilized in most of our patients Fig.

The immunosuppression regimen was switched from CNI to mTOR in patients Nos. Progression of ESRD was unmanageable for patient No.

As children grow up, the kidney is expected to physiologically enlarge. From these observations, LT did reverse nephromegaly, and this may be attributable to the normalized metabolic environment with resolution of dyslipidemia, which was regarded as one of risk factors for nephromegaly [ 6 ].

This study has likewise been consistent in terms of the role of LT in reversing failure-to-thrive, improvement of hepatic function, and reversal of metabolic dysfunction in GSD-I patients [ 7 , 33 ].

Furthermore, neutropenia in the GSD-Ib patient improved after LDLT, implying that correction of liver derangement may have potential benefit with concomitant immune disorder [ 14 ]. Gene therapy, gene editing, and mRNA therapy are new potential strategies for treating genetic diseases [ 34 ]. The liver is an important and common target for such strategies [ 35 ].

Our data indicated that correction of liver derangement by liver targeting may be a critical strategy in preventing complications related to other organs in GSD-I patients. This study has several limitations.

First, we are unable to specifically identify confounding factors associated with renal outcome from our available data, primarily due to early manually recorded information that could not be retrieved from our hospital's previous manual non-electronic medical records, as well as missing parameters from transferred medical records of patients from other hospitals.

Second, the study was conducted at a single medical center, and postoperative prognosis may vary among different hospitals by virtue of differences in management. Third, the GFR was calculated using the updated Schwartz formula for children and the MDRD formula for adults, both of which may overestimate or underestimate the true GFR.

However, we used the formula in both groups for comparability to minimize bias. Fourth, we may underestimate the incidence of AKI because only SCr values were used as the main criterion in the definition of AKI and urinary output was eliminated from the equation.

Finally, the study recruited only 9 GSD-I and 20 BA patients. Therefore, to surpass the limitations, a larger, prospective, randomized controlled trial would be ideal.

Our clinical data demonstrated that post-LT renal function was well preserved in most GSD-I patients. LT cannot reverse the preoperative renal dysfunction but may prevent or slow the progression of albuminuria and CKD. The timepoint of starting cornstarch therapy in GSD-I patients of pre-school age may be critical for long-term renal function.

Early initiation of the treatment results in a good renal prognosis. The dataset supporting the conclusions of this article are included within the article and files. The dataset used during the current study are available from the corresponding author on reasonable request.

Burchell A. Glycogen storage diseases and the liver. Baillieres Clin Gastroenterol. Article CAS PubMed Google Scholar. Chen YT, et al. Renal disease in type I glycogen storage disease.

Authentic Min;QIU Zheng-qing;SONG Hong-mei;ZHAO Shi-min;SHI Hui-ping. Glycogdn Procite. Copyright© by the Editorial Board of Chinese Journal Rneal Nephrology, Chinese Medical Association and the First Affiliated Hospital of Sun Yat-sen University Guangzhou Journal Co. Address: Floor 2, Longzhu building, No. This system is designed and developed by Beijing magtec Technology Development Co. with technical support: support magtech. Open access peer-reviewed chapter. Submitted: 11 Complicatione Reviewed: 28 Sorage Renal complications of glycogen storage disease 08 September Maintain High Levels of Alertness customercare cbspd. Glycogen storage diseases GSDs are genetic diseases affecting the gylcogen, degradation, or utilization of glycogen. Many GSDs comprise stoorage features: GSD Type I can be complicated by tubular anomalies, renal lithiasis, and chronic kidney disease similar to that of diabetes. Fanconi-Bickel syndrome FBS is characterized by hypophosphatemic rickets and a particular tubular dysfunction Fanconi syndromethe most constant element of which is glucosuria. Besides, Tarui disease GSD-VII and McArdle disease GSD-V may be present at the onset in the second decade as an acute renal failure ARF secondary to acute rhabdomyolysis or myoglobinuria.

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