A rare Case presentation (Dr. Mahallawy).pptx

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1. Case Presentation By Mohamed El Mahallawy Assistant professor of Internal Medicine and Nephrology Al- Azhar University Egypt

2. History: Male patient 20 y old , Egyptian student from Cairo ,swimmer ,not smoker ,with no special habits and he is an offspring for consangious marriage (cousins), he has one brother and one sister and they have no evidence of any clinical troubles, he is the youngest member in his family . - The patient presented to our hospital at July 2023 with acute renal shut- down.The acute renal shutdown was associated with mild flank pain and myalgias . - There was a history of a sternous muscular exercise over the last week before the attack as the patient was preparing himself for the Egyptian universities ’ s Swimming Championship

3. No history of fever or other constitutional symptoms. No history recent preceeding or concomitant infection. No history of drug intake . - No history of herbal medications . No history preceeding urinary changes . No family history of renal diseases. No history of previous or recent urological troubles . There was a history of a similar attack at April 2020 and by detailed history from parents they have informed us that serum creatinine has raised up to 3.2 and complete recovery has occurred within two weeks and serum creatinine has landed to the normal level and has remained stable during follow up after discharge for more than 6 months.during that attack no renal biopsy has been taken and no definite diagnosis has been identified.

4. Clinical examination: The patient has a good general condition ,average built but looks ill. fully concious ,oriented for time ,place and persons No pallor ,no jaundice ,no cyanosis No lymphadenopathy No Arthritis No Lower limb edema . Vital signs: Bp150/90 RR 22 TEMP 37 C O2 SAT 98% PULSE 95 b/m regular average volume ,equal in both sides

5. Investigation : CBC: within normal ranges S .Creat 6.5 mg /dl BUN 125 mg/dl S.Uric acid 3.3 mg/dl S.Potassium 5.8 meq /L S.Sodium 130 meq /L S.Phosphorus 4.3 mg /dl S.Calcium 8.9 mg /dl RBS 137 mg/dl CPK : 256 IU/L (2x folds the upper normal range ) ALT 32 U/L AST 29 U/L VBG : PH 7.2 HCO3 13 p CO2 18 Immnolgical profile :withdrawn Serological screening (HBV.HCV.HIV) : negative Abdomenopelvic u/s : unremarkable

6. Mangement : Patient has been admitted in ICU and started to improve as regard clinical and laboratory parameters without need for hemodialysis and has regained adequate urine output within a week from admission and has been transferred to inpatient wards During this week: Urinalysis and Urinary A/C raio has been done : Urinalysis : just albuminuria + Urinary A/C ratio : 550 mg/g - The immunological and virological screen has revealed negative results - Renal biopsy has been taken after stabilization of the patient and we asked the pathologist to finish the result as soon as possible to know the cause and start the specific treatment .

7. During this time we have requested a neurological consultation due to the obvious association between the sternous exercise and the AKI The consultant of Neurology requested the following : - Electromyography : which has shown no abnormality - Muscle biopsy : For exclusion of an occult hereditary muscle disease (Mc Ardle , Pompe or inclusion body myositis ) but unfortunately it was not available at hospital .

8. Based on fluid chart patient has develoed polyuric phase following acute kidney injury and fluid management has been done till complete recovery and patient has been discharged at day 13 from admission . These were the laboratory values at discharge : CBC: within normal ranges S.Creat 0.7 mg /dl BUN 20 mg/dl S.Uric acid 1.6 mg/dl S.Potassium 3.6 meq /L S.Sodium 136 meq /L CPK : 65 IU/L ALT 32 U/L AST 29 U/L

9. Investigation Renal biopsy has been reported the following : Acute Tubular Necrosis with Interstitial Nephritis

10. We have prescribed short term low dose steroids and have instructed the patient to return to our patient clinic for regular follow up. Laboratory values after 1 month follow up : CBC: within normal ranges S.Creat 0.8 mg /dl BUN 25 mg/dl S.Uric acid 1.9 mg/dl S.Potassium 3.8meq/L S.Sodium 135meq/L CPK : 62 IU/L ALT 28 U/L AST 27 U/L Urinary A/C ratio : 290 mg/g Muscle biopsy has been done after discharge and has shown unremarkable findings with no evidence of glycogen storage disease or inclusion body myositis.

11. we have requested a second neurological consultation and he reported that the mild elevation of CPK in not fit for diagnosis of Rhabdomyolysis that is NOT severe enough for affection of the kidneys.So , muscle affection is an association and not a cause of AKI

12. Laboratory values after 3 month of follow up : CBC: within normal ranges S.Creat 1.1 mg /dl BUN 27 mg/dl Urinary A/C ratio : 25 mg/g S.Uric acid 1.6 mg/dl S.Potassium 3.7meq/L S.Sodium 137meq/L CPK : 69 IU/L ALT 27 U/L AST 29 U/L

13. What is the provisional diagnosis and diagnostic approach for our case?

14. Obviously , we have a case of exercise-induced acute kidney injury (EIAKI ) No clinical or laboratory evidence of Rhabdomyolysis We have a fixed hypouricaemia at follow up

15. What is the next step?

16. The next step is to confirm that it is a hyperuricosuric hypouricaemia The following has been requested : - 24 Urinary Uric Acid level : > 8000 mg (normal level is 250 – 750mg / 24 hours) - fractional excretion of uric acid ( FE-UA) was 195% ( normal reference range 5.5–11.1%)

17. Putting in mind the young age of the patient and that most of causes of hyperuricosuric hypouricaemia are genetic causes , so we have asked for a genetic consultation by a Geneticist which has confirmed the indication for genetic counselling Exosomal sequencing has been done .

18. Case discussion and mini-review

19. Hyperuricaemia is a well known risk factors for acute ana chronic kidney diseases as : Acute uric acid (gouty) nephropathy AKI due to Heat Stroke which has been increased due to world wide climate changes (global warming) which is mediated by high serum uric acid level due to dehydration Some tropical renal diseases as Meso -American Nephropathy (Johnson et al.,2013)

20. Surprisingly, on other hand hypouricaemia also is known to be a high risk factor for renal diseases as serum uric acid has a potent anti-oxidant effect which is lost in cases of severe hypouricaemia leading to relaease of reactive oxygen species (ROS ), Inflammasomes which lead to acute tubular injury ,endothelial dysfunction and severe vasoconstriction (Park et al., 2020)

21. So, the relation between the uric acid and kidney is a neutral diplomatic relation and the ideal situation for both is the normal level of serum creatinine and normal renal function . The effect of serum uric acid on the kidney has a U-shaped association ,not a linear association .

22. Renal Hypouricemia Type 1 : Gene: SLC22A12 (URAT1) Protein: solute carrier family 22, member 12 Renal Hypouricemia Type 2: Gene:   SLC2A9 (GLUT9) Protein: solute carrier family 2, facilitated glucose transporter member 9 Impaired reabsorption of uric acid by the kidney leading to : Decreased serum uric acid level of less than 2.0 mg/ dL (<119 umol /L) Increased fractional excretion of uric acid (FEUA) of greater than 10% Heterozygous cases are asymptomatic as the patient is protected by the normal allele Homozygous cases are symptomatic Some have urolithiasis Many cases are presented by exercise-induced acute kidney injury (EI-AKI ) due to over-production of serum uric acid. Hypouricaemia may be masked by diminished GFR in cases of AKI. Renal hypouricaemia may be suspected if there is low normal serum uric acid inspite of severe renal affection . ( Mazzierli et al 2023)

23. What is the optimal line of management in our case ?

24. 1- We have advised the patient to avoid severe muscular exercise and dehydration It was a so difficult mission to tell this insruction for a swimming champion 2- Hypouricaemic agents : Allopurinol 3- Vitamin C 4- Vitamin E 5- Nutritional consultation to start low purine diet (Nakayama   et al., 2019)

25. Future directions

26. In the near future gene editing by CRISPR-Cas9 will make the genetic diseases curable especially after the use of artificial intelligence (AI) in the field of Genomics

27. Lessons from the case ?

28. We should never depend on patient ’ s laboratory values during the early stage of AKI as most of these values are changed by diminished GFR. Follow up of AKI cases after hospital discharge is as an important as management during admition to calarify the cause . Genetic kidney disease may be presents at any age . Multidisciplinary team is very important in management of n ephrological cases. As we consider Genetic counselling in cases of chronic cases of unkown aetiology ( CKDu ), we should also consider it in young paients with AKI who has fixed electrolyte or solute imbalance with no obvious cause.

29. Recommenations ?

30. Arab populations are at high risk for genetic kidney diseases as consangious marriage and environmental changes and its effect on epigenetics We should change our Myths about Nephrogenetics : - Nephrogenetics not usually presented by syndromes -Role of nephrogenetics is not only confined for diagnosis of inherited diseases but it is a main player in all fields of Nephrology ( predisposition for AKI , risk for Diabetic kidney disease, decisions for drugs in FSGS, role in vascular calcifications in CKD (Klotho gene ) ,donor selection in renal transplantation , expecting outcume in renal transplantation in Alport disease and recently a great role in Xenograft ) There is an emerging era of gene editing tool, personalized medicine and new use of artificial intelligence (AI) in genetics . So, we recommend more focus on the area of Nephrogenetics in the era of Nephrology subspecialities .

31. Home massage

32. Inspite of great advances in the field of Nephrology , genetic kidney diseases are still underestimated and underdefined and genetic kidney diseases cases will remain a very challenging cases which and nephrogenetics ’ zone is still the mysterious and dark zone in Nephrology

33. THANK YOU