Medical Faculty of Ruperto Carola University Heidelberg

Medical Faculty of RupertoCarola University Heidelberg:“A look back one and a halfcenturies"Professor Dr. Eberhard RitzUniversity of Heidelberg – NierenzentrumHeidelberg, Germany

History of Medical School in Heidelberg

Heidelberg Medical School1378Schisma [German students no longer admitted tio Sorbonne (Paris)]4 faculties: Theology, Medicine, Law and ArtsRuprecht I.Prince Electorand Count Palatine(Ruperto-Carola)First rectorMarsilius von Inghen(Nijmegen)

1686 Conrad Brunner “Brunner‘s glands“Heidelberg destroyed by Louis Quatorze in 1689University rebuilt“Alte Universität“

Medical faculty 19th centuryHermann von Helmholtz (1821-1894) ophthalmoscopeTrio: Helmholtz(physiologist), Bunsen (chemist),Kirchhof (physicist)Jakob Henle (1809-1885) Henle‘s loopVincent Czerny (1842-1916) oncology (leukemia)Erb Wilhelm (1840-1921) neurology (dystrophy, palsy…)Friedreich Nicolaus (1825-1882) neurology (ataxia,…)Kussmaul Adolf (1822-1902) internist, (periarteritis nodosa,Kussmaul respiration, Kussmaul pulse (p.paradoxus)…

Nobel prizesHans Jensen 1963(1907-1973)shell model of atomic nucleusGeorg Wittig 1979 synthesis of complex organic compounds(1897-1987) (“Wittig reaction”)Bert Sakmann 1991(1942-…)Harald zur Hausen 2008(1936-…)cellular ion channelspapillomavirus and cervical cancer

Gustav Simon(1824-1870)after animal experiments first nephrectomy of kidney with malignancyApril 2 nd 1869 in Meckesheim

Amphibian kidney to poove that tubular dropletsare caused by protein uptakeTubular degeneration with hyaline droplets (T)in the proximal tubular epithelial cellsEdmund Randerath1899-1961consequence and not cause ofnephrotic proteinuria

Axolotl(Ambystoma mexicanum)i.p.injection of albumintubulusdrainingglomerularfiltratetubulusdrainingperitonealcavityglycated albumin more nephrotoxicGross, Am.J.Physiol.(2011) 301:F476

Interstitial fibrosismost significant correlate to serum creatinines-creatinine(mg/dl)relative interstitial volume(%)Bohle A., Virchows Archiv A, (1977) 373:15-22

Horst Bickel(1918-2000)PediatricsPhenylketonuriaDietary management

Enjoy your stay in Heidelberg

Bariatric surgery –one potential renal problem,RYGB(Roux en Y bypass)

Terminal renal failure of a diabetic patient after “gastric bypass“ surgery; Qadri et al; St.Paul (USA)# 52- year old female patient with type 2 diabetes and hypertension# 2 years ago CKD stage 1 and Roux-en-Y “gastric bypass”# Admission without symptoms of uremia :S-creatinine 4,5 mg/dl; eGFR 10,9 ml/min./1.72 m 2 ,bicarbonate 18 mmol/L, S-K + 3,6 mmol/L# kidney ultrasound unremarkable# start of hemodialysis and : kidney biopsywhat do you expect to find in the renal biopsy ?

Terminal Renal Failure of a Diabetic Patient after “gastric bypass“ surgery; Qadri et al; St.Paul (USA)# Initial stage of diabetic nephropathy, negative immune fluorescence,massive oxalate deposits in tubular lumina# Plasma oxalate concentration 17 μmol/L (normal: < 1,8);Urinary oxalate excretion 53,2 mg/g creatinine (normal:1,6-37);fat in feces: 8g/72 h.

Diffuse tubular degenerative changesintracellular + intraluminalcalcium oxalate depositsSame, polarized lightCa oxalate depositshigh magnificationNasr, CJASN (2008) 3:1676Degenerative changes,(e.g. luminal ectasia,cytoplasmic simplification,loss of brush border)

Fat malabsorptionAs a result, calcium binds free fatty acidsOxalate is no longer sufficiently bound and precipitated by calciumIncreased intestinal oxalate absorptionHyperoxaluria causing renal oxalosisManagement :low dietary oxalate intakelow fat dietcalcium supplementsnot all renal failure in type 2 diabetes is the result ofdiabetic nephropathyafter “gastric bypass“ consider secondary oxalosis !

Pathogenesis of oxalate stones andrenal oxalosis after bariatric surgerySaponification of calcium as result of fat malabsorptionreduced binding of oxalate to calcium,Increased permeability of colon mucosa, result ofupstream decreased bile salt absorptionescape of oxalate into blood streamColonisation of colon mucosa by oxalobacter formigenesreduced after antibiotic therapyadministration of oxalobacter reduces oxalate blood concentrationAdministration of vitamin C may cause oxalate nephropathy

Main threat to kidney after bariatric surgery:high prevalence of hyperoxalurianephrolithiasis, oxalosishigh prevalence early on in the 1970ies: 39% after 15 year follow-up,today much decreasedClayman, Surg.Clin.North.Amer. (1979)59:1071increasing with time after surgeryMiller, J.Urol.(2008) 179:4033% stones within first 180 daysEncinosa, Med.Care(2006) 44:70610 fold higher in patients with history of nephrolithiasisDurrani, J.Endourol.(2006) 20:749

Bariatric surgery : renal effectsZalesin K.C.,McCulloughBariatric surgery for morbid obesity: risks and benefits in chronic kidney diseasepatientsAdv.Chron.Kidn.Dis(2006);13:403-17Currie A, Chetwood A, Ahmed AR.Baritaric surgery and kidney functionObes Surg. (2011) 21:528beneficial : reduction of albuminuria/proteinuriaadverse: oxalate nephrolithiasis and renal oxalosis

Prophylactic dietary modification is the current best strategy.Maintenance of a low oxalate dietin combination with calcium supplements (as an oxalate binding agent)has been shown to be effective in protecting post-RYGB patients withenteric hyperoxaluria from developing nephrolithiasis in a retrospectivestudy.Future studies will focus on the potential of Oxalobacteras a potential therapy to prevent theoccurrence of kidney stones in this at-risk population.Andrew Currie, Andrew Chetwood, Ahmed R. AhmedBariatric Surgery and Renal FunctionObesity Surgery (2011) 21:528