William H. Fissell, IV, M.D.

Associate Professor of Medicine


Nephrology and Hypertension


M.D. - Case Western Reserve University

Office Address:
1161 21st Ave. South, MCN, Room / Suite S3223, Nashville, TN 37232

William H. Fissell, IV, M.D.

Research Description 

Detailed Analysis of therapeutic strategy in AKI

We continue to be puzzled by the limited benefit or even harm associated with increased dialysis dose in AKI, as seen in the Tolwani, ATN, and RENAL trials. How could these studies fail to show a benefit, when the earlier Ronco, Saudan, and possibly the Bouman trials showed improved long-term survival with prescription of 35-45 ml/kg/hour of therapy? Two general sets of hypotheses suggested themselves. First, is it possible that the newer studies of CVVHDF were somehow different from the earlier studies of CVVH, and in one case, CVVH vs CVVHDF? Using bovine blood and techniques similar to those used to test performance of novel hemofilters, we determined that middle molecule clearance in CRRT is a strong function of membrane area and relatively insensitive to prescribed mode of therapy (PMID 19282753). We went on to measure middle molecule clearance at 20 versus 35 ml/kg/hour CVVHDF and found that there was negligible difference in middle molecule clearance between the two arms (PMID 20016150). This suggests that the treatment arms in early studies differed in both small-molecule and middle molecule clearance, while later studies varied small molecule clearance while inadvertently holding middle molecule clearance constant. We are in the planning stages of a study varying middle molecule clearance while holding small solute clearance constant. 

Clinical Interest 

Technology Development for End-Stage Renal Disease

Maintenance dialysis prescriptions have come to target frequent and prolonged therapy. Prolonged dialysis appears to confer significant clinical benefit in cardiac, nutritional, and endocrine health. The existing infrastructure of dialysis clinics cannot expand in capacity to deliver prolonged daily therapy to all patients, and home-based dialysis has only penetrated 0.5% of the US market. The rate limiting factor in uptake of home-based intensive maintenance dialysis appears to be patient concerns about safety of the therapy and burden on family members. Reconfiguring delivery of ESRD care to resemble the AICD model for cardiac rhythm management based on an autonomous implanted device would facilitate adoption of intensive therapies. An implanted device internalizes the blood circuit, minimizing risk of accidental disconnect, and locates infection-prone percutaneous connections on the traditionally nonsterile dialysate side of the circuit. Wearable therapies in development appear to require long-term percutaneous vascular or peritoneal access, with attendant worries regarding infection and accidental disconnection. Hollow-fiber membranes have limited service lifetime and require significant energy to propel fluid – be it blood or dialysate – through the cartridge, precluding use in implanted devices. Therefore, new membranes designed to maximize permeability and selectivity are critical to implementing a fundamentally enabling paradigm shift in ESRD care. 

Research Keywords 

Epithelial cell culture tissue engineering bioartificial kidneys


Fissell WH. Introduction to Making Dialysis Adequate-Addressing its Limitations. Semin Dial [print-electronic]. 2016 Nov; 29(6): 423-4. PMID: 27678202, DOI: 10.1111/sdi.12545, ISSN: 1525-139X.

Shotwell MS, Nesbitt R, Madonia PN, Gould ER, Connor MJ, Salem C, Aduroja OA, Amde M, Groszek JJ, Wei P, Taylor ME, Tolwani AJ, Fissell WH. Pharmacokinetics and Pharmacodynamics of Extended Infusion Versus Short Infusion Piperacillin-Tazobactam in Critically Ill Patients Undergoing CRRT. Clin J Am Soc Nephrol [print-electronic]. 2016 Aug 8/8/2016; 11(8): 1377-83. PMID: 27197907, PMCID: PMC4974884, PII: CJN.10260915, DOI: 10.2215/CJN.10260915, ISSN: 1555-905X.

Vijayan A, Faubel S, Askenazi DJ, Cerda J, Fissell WH, Heung M, Humphreys BD, Koyner JL, Liu KD, Mour G, Nolin TD, Bihorac A, . Clinical Use of the Urine Biomarker [TIMP-2] × [IGFBP7] for Acute Kidney Injury Risk Assessment. Am. J. Kidney Dis [print-electronic]. 2016 Jul; 68(1): 19-28. PMID: 26948834, PMCID: PMC4921267, PII: S0272-6386(16)00141-4, DOI: 10.1053/j.ajkd.2015.12.033, ISSN: 1523-6838.

Kensinger C, Karp S, Kant R, Chui BW, Goldman K, Yeager T, Gould ER, Buck A, Laneve DC, Groszek JJ, Roy S, Fissell WH. First Implantation of Silicon Nanopore Membrane Hemofilters. ASAIO J. 2016 Jul; 62(4): 491-5. PMID: 26978710, PMCID: PMC4983406, DOI: 10.1097/MAT.0000000000000367, ISSN: 1538-943X.

Kim S, Heller J, Iqbal Z, Kant R, Kim EJ, Durack J, Saeed M, Do L, Hetts S, Wilson M, Brakeman P, Fissell WH, Roy S. Preliminary Diffusive Clearance of Silicon Nanopore Membranes in a Parallel Plate Configuration for Renal Replacement Therapy. ASAIO J. 2016 Mar; 62(2): 169-75. PMID: 26692401, PMCID: PMC4777646, DOI: 10.1097/MAT.0000000000000311, ISSN: 1538-943X.

Shotwell MS, Zhou M, Fissell WH. Optimal design of perturbations for individual two-compartment pharmacokinetic analysis. J Biopharm Stat [print-electronic]. 2016; 26(5): 803-15. PMID: 26247447, PMCID: PMC4744591, DOI: 10.1080/10543406.2015.1074918, ISSN: 1520-5711.

Kim S, Feinberg B, Kant R, Chui B, Goldman K, Park J, Moses W, Blaha C, Iqbal Z, Chow C, Wright N, Fissell WH, Zydney A, Roy S. Diffusive Silicon Nanopore Membranes for Hemodialysis Applications. PLoS ONE. 2016; 11(7): e0159526. PMID: 27438878, PMCID: PMC4954641, PII: PONE-D-16-08708, DOI: 10.1371/journal.pone.0159526, ISSN: 1932-6203.

de Caestecker M, Humphreys BD, Liu KD, Fissell WH, Cerda J, Nolin TD, Askenazi D, Mour G, Harrell FE, Pullen N, Okusa MD, Faubel S, . Bridging Translation by Improving Preclinical Study Design in AKI. J. Am. Soc. Nephrol [print-electronic]. 2015 Dec; 26(12): 2905-16. PMID: 26538634, PMCID: PMC4657852, PII: ASN.2015070832, DOI: 10.1681/ASN.2015070832, ISSN: 1533-3450.

Shotwell MS, Madonia PN, Connor MJ, Amde M, Salem C, Aduroja OA, Bauer SR, Groszek JJ, Fissell WH. Ciprofloxacin pharmacokinetics in critically ill patients receiving concomitant continuous venovenous hemodialysis [letter]. Am. J. Kidney Dis [print-electronic]. 2015 Jul; 66(1): 173-5. PMID: 25912840, PII: S0272-6386(15)00522-3, DOI: 10.1053/j.ajkd.2015.03.001, ISSN: 1523-6838.

Ferrell N, Sandoval RM, Bian A, Campos-Bilderback SB, Molitoris BA, Fissell WH. Shear stress is normalized in glomerular capillaries following ¿ nephrectomy. Am. J. Physiol. Renal Physiol [print-electronic]. 2015 Mar 3/15/2015; 308(6): F588-93. PMID: 25587117, PMCID: PMC4360039, PII: ajprenal.00290.2014, DOI: 10.1152/ajprenal.00290.2014, ISSN: 1522-1466.

Demirjian S, Fissell WH. Staying on target with continuous dialysis [editorial]. Clin J Am Soc Nephrol [print-electronic]. 2015 Jan 1/7/2015; 10(1): 7-8. PMID: 25538268, PMCID: PMC4284419, PII: CJN.11251114, DOI: 10.2215/CJN.11251114, ISSN: 1555-905X.

Fissell WH. Laboratory assays in renal failure: therapeutic drug monitoring. Semin Dial [print-electronic]. 2014 Nov; 27(6): 614-7. PMID: 24995571, DOI: 10.1111/sdi.12279, ISSN: 1525-139X.

Olorunsola OG, Kim SH, Chang R, Kuo YC, Hetts SW, Heller A, Kant R, Saeed M, Fissell WH, Roy S, Wilson MW. Imaging assessment of a portable hemodialysis device: detection of possible failure modes and monitoring of functional performance. Med Instrum (Luton). 2014 Mar 3/27/2014; 2(2): PMID: 25045526, PMCID: PMC4101171, DOI: 10.7243/2052-6962-2-2.                        

Golper TA, Fissell R, Fissell WH, Hartle PM, Sanders ML, Schulman G. Hemodialysis: core curriculum 2014. Am. J. Kidney Dis [print-electronic]. 2014 Jan; 63(1): 153-63. PMID: 24268927, PMCID: PMC4276338, PII: S0272-6386(13)01318-8, DOI: 10.1053/j.ajkd.2013.07.028, ISSN: 1523-6838. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24268927., 2014.

Afshartous D, Bauer SR, Connor MJ, Aduroja OA, Amde M, Salem C, Groszek JJ, Fissell WH. Pharmacokinetics and pharmacodynamics of imipenem and meropenem in critically ill patients treated with continuous venovenous hemodialysis [letter]. Am. J. Kidney Dis [print-electronic]. 2014 Jan; 63(1): 170-1. PMID: 24145021, PII: S0272-6386(13)01201-8, DOI: 10.1053/j.ajkd.2013.08.015, ISSN: 1523-6838. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24145021., 2014.

Humes HD, Buffington D, Westover AJ, Roy S, Fissell WH. The bioartificial kidney: current status and future promise. Pediatr. Nephrol [print-electronic]. 2014 Mar; 29(3): 343-51. PMID: 23619508, DOI: 10.1007/s00467-013-2467-y, ISSN: 1432-198X. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23619508., 2014.

Fissell WH. Antimicrobial dosing in acute renal replacement. Adv Chronic Kidney Dis. 2013 Jan; 20(1): 85-93. PMID: 23265600, PMCID: PMC3807249, PII: S1548-5595(12)00194-2, DOI: 10.1053/j.ackd.2012.10.004, ISSN: 1548-5609. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23265600., 2013.

Garg N, Fissell WH. Intradialytic hypotension: a case for going slow and looking carefully. Nephrol. Dial. Transplant [print-electronic]. 2013 Feb; 28(2): 247-9. PMID: 22848109, PII: gfs316, DOI: 10.1093/ndt/gfs316, ISSN: 1460-2385. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22848109., 2013.

Ferrell N, Cameron KO, Groszek JJ, Hofmann CL, Li L, Smith RA, Bian A, Shintani A, Zydney AL, Fissell WH. Effects of pressure and electrical charge on macromolecular transport across bovine lens basement membrane. Biophys. J. 2013 Apr 4/2/2013; 104(7): 1476-84. PMID: 23561524, PMCID: PMC3617438, PII: S0006-3495(13)00261-0, DOI: 10.1016/j.bpj.2013.01.062, ISSN: 1542-0086. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23561524., 2013.

Fissell WH, Roy S, Davenport A. Achieving more frequent and longer dialysis for the majority: wearable dialysis and implantable artificial kidney devices. Kidney Int [print-electronic]. 2013 Aug; 84(2): 256-64. PMID: 23407434, PII: ki2012466, DOI: 10.1038/ki.2012.466, ISSN: 1523-1755. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23407434., 2013.

Fissell WH. What is nanotechnology? [editorial]. Adv Chronic Kidney Dis. 2013 Nov; 20(6): 452-3. PMID: 24206597, PII: S1548-5595(13)00129-8, DOI: 10.1053/j.ackd.2013.08.008, ISSN: 1548-5609. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24206597., 2013.

Ferrell N, Ricci KB, Groszek J, Marmerstein JT, Fissell WH. Albumin handling by renal tubular epithelial cells in a microfluidic bioreactor. Biotechnol. Bioeng [print-electronic]. 2012 Mar; 109(3): 797-803. PMID: 22012446, PMCID: PMC3285552, DOI: 10.1002/bit.24339, ISSN: 1097-0290. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22012446., 2012.

Fissell WH. Illuminating the glomerular filtration barrier, two photons at a time [editorial]. J. Am. Soc. Nephrol [print-electronic]. 2012 Mar; 23(3): 373-5. PMID: 22323639, PII: ASN.2012010067, DOI: 10.1681/ASN.2012010067, ISSN: 1533-3450. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22323639., 2012.

Bauer SR, Salem C, Connor MJ, Groszek J, Taylor ME, Wei P, Tolwani AJ, Fissell WH. Pharmacokinetics and pharmacodynamics of piperacillin-tazobactam in 42 patients treated with concomitant CRRT. Clin J Am Soc Nephrol [print-electronic]. 2012 Mar; 7(3): 452-7. PMID: 22282479, PMCID: PMC3302674, PII: CJN.10741011, DOI: 10.2215/CJN.10741011, ISSN: 1555-905X. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22282479., 2012.

Smith RA, Fissell WH, Fleischman AJ, Zorman CA. A low-cost automated streaming potential measurement system. J Lab Autom [print-electronic]. 2012 Apr; 17(2): 125-33. PMID: 22357558, PII: 2211068211425663, DOI: 10.1177/2211068211425663, ISSN: 2211-0682. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22357558., 2012.

Neuner EA, Ahrens CL, Groszek JJ, Isada C, Vogelbaum MA, Fissell WH, Bhimraj A. Use of therapeutic drug monitoring to treat Elizabethkingia meningoseptica meningitis and bacteraemia in an adult. J. Antimicrob. Chemother [print-electronic]. 2012 Jun; 67(6): 1558-60. PMID: 22357803, PMCID: PMC3350328, PII: dks053, DOI: 10.1093/jac/dks053, ISSN: 1460-2091. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22357803., 2012.

Ferrell N, Groszek J, Li L, Smith R, Butler RS, Zorman CA, Roy S, Fissell WH. Basal lamina secreted by MDCK cells has size- and charge-selective properties. Am. J. Physiol. Renal Physiol [print-electronic]. 2011 Jan; 300(1): F86-90. PMID: 20980405, PMCID: PMC3023222, PII: ajprenal.00484.2010, DOI: 10.1152/ajprenal.00484.2010, ISSN: 1522-1466. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20980405., 2011.

Connor MJ, Salem C, Bauer SR, Hofmann CL, Groszek J, Butler R, Rehm SJ, Fissell WH. Therapeutic drug monitoring of piperacillin-tazobactam using spent dialysate effluent in patients receiving continuous venovenous hemodialysis. Antimicrob. Agents Chemother [print-electronic]. 2011 Feb; 55(2): 557-60. PMID: 21115798, PMCID: PMC3028791, PII: AAC.00548-10, DOI: 10.1128/AAC.00548-10, ISSN: 1098-6596. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21115798., 2011.

Muthusubramaniam L, Lowe R, Fissell WH, Li L, Marchant RE, Desai TA, Roy S. Hemocompatibility of silicon-based substrates for biomedical implant applications. Ann Biomed Eng [print-electronic]. 2011 Apr; 39(4): 1296-305. PMID: 21287275, PMCID: PMC3069312, DOI: 10.1007/s10439-011-0256-y, ISSN: 1573-9686. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21287275., 2011.

Bauer SR, Culver DA, Abraham S, Lam SW, Fissell WH, Wiedemann HP, Reddy AJ. Detectability of vasopressin in continuous venovenous hemodialysis effluent of patients with vasodilatory shock treated with exogenous arginine vasopressin. Pharmacotherapy. 2011 Sep; 31(9): 857-62. PMID: 21923586, DOI: 10.1592/phco.31.9.857, ISSN: 1875-9114. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21923586., 2011.

Roy S, Goldman K, Marchant R, Zydney A, Brown D, Fleischman A, Conlisk A, Desai T, Duffy S, Humes H, Fissell W. Implanted renal replacement for end-stage renal disease. Panminerva Med. 2011 Sep; 53(3): 155-66. PMID: 21775942, PII: R41112615, ISSN: 1827-1898. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21775942., 2011.

Axelsson J, Sverrisson K, Rippe A, Fissell W, Rippe B. Reduced diffusion of charge-modified, conformationally intact anionic Ficoll relative to neutral Ficoll across the rat glomerular filtration barrier in vivo. Am. J. Physiol. Renal Physiol [print-electronic]. 2011 Oct; 301(4): F708-12. PMID: 21775478, PII: ajprenal.00183.2011, DOI: 10.1152/ajprenal.00183.2011, ISSN: 1522-1466. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21775478., 2011.

Demirjian S, Teo BW, Guzman JA, Heyka RJ, Paganini EP, Fissell WH, Schold JD, Schreiber MJ. Hypophosphatemia during continuous hemodialysis is associated with prolonged respiratory failure in patients with acute kidney injury. Nephrol. Dial. Transplant [print-electronic]. 2011 Nov; 26(11): 3508-14. PMID: 21382993, PII: gfr075, DOI: 10.1093/ndt/gfr075, ISSN: 1460-2385. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21382993., 2011.

Groszek J, Li L, Ferrell N, Smith R, Zorman CA, Hofmann CL, Roy S, Fissell WH. Molecular conformation and filtration properties of anionic Ficoll. Am. J. Physiol. Renal Physiol [print-electronic]. 2010 Oct; 299(4): F752-7. PMID: 20668097, PII: ajprenal.00324.2010, DOI: 10.1152/ajprenal.00324.2010, ISSN: 1522-1466. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20668097., 2010.

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